Efficacy of treatments for pain and numbness in cancer survivors: a systematic review and meta-analysis.

BACKGROUND: Pain and numbness in cancer survivors frequently have negative impacts on quality of life (QoL). This meta-analysis aimed to identify the current treatment options for pain and numbness in cancer survivors and to evaluate their effects. METHODS: Cancer survivors were defined as patients diagnosed with cancer who had completed active cancer treatment, whose conditions were stable, and who had no evidence of recurrent or progressive disease. A systematic search through the PubMed, MEDLINE, Embase, Cochrane Central Register of Controlled Trials, Web of Science, PsycInfo, and CINAHL databases was conducted, which targeted randomized controlled trials (RCTs) published until April 2022 that evaluated any type of treatment for pain or numbness in cancer survivors. A meta-analysis was conducted using the random-effects model to obtain the effect sizes of 7 types of treatments: opioid therapy, nonopioid pharmacotherapy, interventional therapy, acupuncture, education/cognitive behavioral therapy (CBT), physical exercise, and alternative medicine. RESULTS: A total of 36 studies involving 2,870 cancer survivors were included. Among them, 35 (n=2,813) were included in the meta-analysis for pain. The analysis suggested that physical exercise [n=761; 13 studies; standardized mean difference (SMD) -0.84; 95% confidence interval (CI): -1.14 to -0.55], acupuncture (n=409; 3 studies; SMD -0.80; 95% CI: -1.04 to -0.56), and alternative medicine (n=206; 6 studies; SMD -0.44; 95% CI: -0.71 to -0.16) could significantly reduce pain. Nonopioid pharmacotherapy and education/CBT did not demonstrate significant effects. No studies were identified that investigated the effects of opioid therapy or interventional therapy on pain. Regarding numbness, 5 studies (n=566) were included in the meta-analysis. Acupuncture (n=99; 2 studies) did not demonstrate significant effects on numbness, and the effects of nonopioid pharmacotherapy, education/CBT, and physical exercise could not be determined due to the small number of included studies. No studies were identified that investigated the effects of opioid therapy, interventional therapy, or alternative medicine on numbness. CONCLUSIONS: This meta-analysis suggested that physical exercise, acupuncture, and alternative medicine may reduce pain in cancer survivors, with a very small to moderate amount of evidence. The effect of treatments for numbness could not be determined due to the limited number of included studies. Further studies are needed, particularly on widely used pharmacotherapy.

Imaging features inferring symptom onset due to spinal metastasis progression: a preliminary study.

BACKGROUND: Spinal metastases can cause intractable pain and neurological deficits, which can markedly worsen both patients' activities of daily living (ADL) and their health-related quality of life (QOL). Early intervention is essential to prevent irreversible neurological deficits and pain associated with spinal metastases. We investigated the imaging features of spinal metastases that led to neurological deficits. METHODS: We analyzed axial cross-sectional computed tomography (CT) images of cervical and thoracic spinal metastases in patients with and without lower limb motor paralysis, neuropathic pain, and local nociceptive pain. We distinguished regions of the spine associated with these respective symptoms, and explored their inferable performance using images obtained before symptom onset. In addition, we analyzed the imaging features and type of bone metastasis (osteolytic and osteoblastic). RESULTS: Spinal lesions occupied the area in and around the spinal canal and around the pedicle in patients with motor paralysis. Lesions around the pedicle and in the most posterior vertebral body part before symptom onset were inferable. In patients with neuropathic pain, spinal metastases spread along the pedicle before symptom onset, and had surrounded the spinal canal circumferentially at symptom onset. Local nociceptive pain was more common near the center of the vertebral body either at or before symptom onset. There was no difference in the imaging features according to the type of bone metastasis. CONCLUSIONS: Lesions in certain regions in the asymptomatic metastatic spine can indicate the onset of spinal metastasis-related symptoms in the next few months. Early therapeutic intervention might be applied to prevent neurological disorder.

Prefectural Adequacy of Opioid Availability for Cancer Pain and Its Determinants in Japan: A Preliminary Study.

INTRODUCTION: Opioid analgesics are the mainstay of cancer pain management. The annual opioid consumption globally indicates adequate opioid availability and the quality of palliative care. We investigated the current situation regarding the adequacy of opioid availability in individual prefectures in Japan and explored the determinants of adequacy. METHODS: We analyzed nationwide databases open to public inspection depicting the current Japanese healthcare situation. Opioid consumption for cancer pain was estimated from oxycodone and morphine data in the nationwide database. On the basis of the World Health Organization recommendations, we calculated adequacy based on the annual cancer deaths in each prefecture in 2013 and 2015. We investigated the associations between adequacy and either outpatient medical expenditure for hypertension and diabetes as a proxy of primary care practice or ratios of these risk holders in community. Outpatient medical expenditures for musculoskeletal disorders and neoplasms were also investigated. RESULTS: The nationwide adequacy of opioid availability was approximately 75%. The largest gaps in adequacy between prefectures were more than 65%. The adequacy correlated with expenditure but not local volumes of hypertension and diabetes in both years. The other two expenditures did not relate to opioid availability. CONCLUSIONS: Although precise data are required, our preliminary findings indicate that primary care practice is the key regulator of adequate opioid availability. Opioid adequacy in Japan is thus delayed in matching the global standard, and gaps in opioid adequacy among prefectures should be bridged rapidly to expand universal access to effective palliative care and cancer pain relief.

Clopidogrel, an ADP-P2Y12 Receptor Antagonist, Can Prevent Severe Postoperative Pain: A Retrospective Chart Review.

The purinergic P2Y12 receptor regulates microglial activation, resulting in persistence and aggravation of pain in neuropathic and nociceptive pain models. We conducted a retrospective chart review to explore the analgesic potency of the P2Y12 receptor-specific antagonist, clopidogrel, for clinical management of postoperative pain in patients who underwent abdominal surgery. Twenty-seven patients with cardiovascular comorbidities, who underwent laparoscopic abdominal surgery and had ceased aspirin (ASP, n = 17) or clopidogrel (CLP, n = 10) for 14 days pre-operatively, were enrolled retrospectively. In both groups, the number of opioids and non-steroidal anti-inflammatory drugs (NSAIDs) consumed for managing postoperative pain was compared using the chi-square test and Mann-Whitney test. Our results showed that from postoperative day (POD) 0 to POD 3, the average numerical rating reflecting the postoperative pain was comparable between the two groups (CLP: 4.0 ± 1.4 vs. ASP: 3.7 ± 0.8, P-value = 0.56). However, at POD 7, opioid consumption in the CLP-treated group (fentanyl-equivalent dose: 0.49 ± 0.56 mg) was significantly lower than that in the ASP-treated group (1.48 ± 1.35 mg, P-value = 0.037). After reaching a stable state by repeated systemic administration, clopidogrel sustained the analgesic efficacy for a certain period. In conclusion, microglial P2Y12 receptors may mediate signal transduction of postoperative nociceptive pain and enhance clinical opioid analgesia.

[A Case of an EXIT (Ex-utero Intrapartum Treatment) Procedure for a Fetal Giant Oronasopharyngeal Tumor.]

We report successful anesthetic management of an EXIT (ex-utero intrapartum treatment) procedure for fetal giant oronasopharyngeal tumor. A 34-year-old nul- liparous woman was diagnosed as having a fetus with giant oronasopharyngeal tumor and scheduled for an EXIT procedure at 34 weeks of pregnancy. After induction of general anesthesia and tracheal intubation, 6% desflurane and a moderate dose of remifentanil infusion were started to provide anesthesia for both the mother and the fetus. To achieve sufficient uterine relaxation during an EXIT procedure, desflurane was gradually increased up to 10% and nitroglycerin infu- sion was added just before uterine incision. Maternal blood pressure was maintained with continuous infu- sion of phenylephrine. Fetal monitoring during an EXIT procedure was performed with an electrocar- diogram using needle electrodes in addition to trans- thoracic echocardiography. No additional anesthetics were necessary for fetal immobilization. After the completion of tracheostomy followed by the separation of the fetus, nitroglycerin and desflurane were discon- tinued and adequate uterine tone was soon obtained. Maintenance of anesthesia was achieved with propofol and remifentanil for the remaining of the operation. The postoperative course was uneventful. The impor- tance of preoperative detailed simulation and discussion about the procedure among multidisciplinary team members was reconfirmed.