In patients with unresectable hepatocellular carcinoma (HCC) without both macrovascular invasion and extrahepatic metastasis, the initial treatment choice recommended is transarterial chemoembolization (TACE). Before sorafenib came into wide use, TACE had been pointlessly carried out repeatedly. It was in the early 2010s that the concept of TACE refractory was advocated. Two retrospective studies from Japan indicated that conversion from TACE to sorafenib the day after patients were deemed as TACE refractory improved overall survival compared with continued TACE, according to the definition by the Japan Society of Hepatology. Nowadays, phase 3 trials have shown clinical benefits of several novel molecular target agents. Compared with the era of sorafenib, sequential treatments with these molecular target agents have gradually prolonged patients’ survival and have become major strategies in patients with HCC. Taking these together, conversion from TACE to systemic therapies at the time of TACE refractory, compared with before, may have a greater impact on survival and may be considered deeper in the decisions-making process in patients with unresectable HCC who are candidate for TACE. Up-to-date information on the concept of TACE refractory is summarized in this review. We believe that the survival of patients with unresectable HCC without both macrovascular invasion and extrahepatic metastasis may be dramatically improved by optimal timing of TACE refractory and switching to systemic therapies.

PURPOSE: Bupivacaine is commonly used for the treatment of back pain and the diagnosis of its origin. Nonunion is sometimes observed after spinal fusion surgery; however, whether the nonunion causes pain is controversial. In the current study, we aimed to detect painful nonunion by injecting bupivacaine into the disc space of patients with nonunion after anterior lumbar interbody fusion (ALIF) surgery for discogenic low back pain. MATERIALS AND METHODS: From 52 patients with low back pain, we selected 42 who showed disc degeneration at only one level (L4-L5 or L5-S1) on magnetic resonance imaging and were diagnosed by pain provocation on discography and pain relief by discoblock (the injection of bupivacaine). They underwent ALIF surgery. If the patients showed low back pain and nonunion 2 years after surgery, we injected bupivacaine into the nonunion disc space. Patients showing pain relief after injection of bupivacaine underwent additional posterior fixation using pedicle screws. These patients were followed up 2 years after the revision surgery. RESULTS: Of the 42 patient subjects, 7 showed nonunion. Four of them did not show low back pain; whereas 3 showed moderate or severe low back pain. These 3 patients showed pain reduction after injection of bupivacaine into their nonunion disc space and underwent additional posterior fixation. They showed bony union and pain relief 2 years after the revision surgery. CONCLUSION: Injection of bupivacaine into the nonunion disc space after ALIF surgery for discogenic low back pain is useful for diagnosis of the origin of pain.
Back Pain ; Bupivacaine* ; Diagnosis ; Humans ; Intervertebral Disc ; Intervertebral Disc Degeneration ; Low Back Pain* ; Magnetic Resonance Imaging ; Methods ; Spinal Fusion ; Spine

PURPOSE: Opioids improve pain from knee and hip osteoarthritis (OA) and decrease the functional impairment of patients. However, there is a possibility that opioids induce analgesia and suppress the physiological pain of OA in patients, thereby inducing the progression of OA changes in these patients. The purpose of the current study was to investigate the possibility of progressive changes in OA among patients using opioids. MATERIALS AND METHODS: Two hundred knee or hip OA patients were evaluated in the current prospective, randomized, active-controlled study. Patients were randomized 1:1:1 into three parallel treatment groups: loxoprofen, tramadol/acetaminophen, and transdermal fentanyl groups. Medication was administered for 12 weeks. Pain scores and progressive OA changes on X-ray films were evaluated. RESULTS: Overall, pain relief was obtained by all three groups. Most patients did not show progressive OA changes; however, 3 patients in the transdermal fentanyl group showed progressive OA changes during the 12 weeks of treatment. These 3 patients used significantly higher doses than others in the transdermal fentanyl group. Additionally, the average pain score for these 3 patients was significantly lower than the average pain score for the other patients in the transdermal fentanyl group. CONCLUSION: Fentanyl may induce progressive changes in knee or hip OA during a relatively short period, compared with oral Non-Steroidal Anti-Inflammatory Drugs or tramadol.
Aged ; Aged, 80 and over ; Analgesics, Opioid/*adverse effects/therapeutic use ; Disease Progression ; Female ; Fentanyl/*adverse effects/therapeutic use ; Humans ; Male ; Middle Aged ; Osteoarthritis, Hip/*drug therapy/radiography ; Osteoarthritis, Knee/*drug therapy/radiography ; Pain/drug therapy

PURPOSE: Surgery for lumbar spinal degeneration disease is widely performed. While posterior decompression and fusion are popular, anterior lumbar interbody fusion (ALIF) is also used for treatment. Extreme lateral interbody fusion (XLIF) is commonly used for noninvasive ALIF; however, several complications, such as spinal nerve and psoas muscle injury, have been reported. In the current study, we examined the clinical efficacy and complications of oblique lateral interbody fusion (OLIF) for lumbar spinal degeneration disease. MATERIALS AND METHODS: Thirty-five patients with degenerated spondylolisthesis, discogenic pain, and kyphoscoliosis were examined. All patients underwent OLIF surgery (using a cage and bone graft from the iliac crest) with or without posterior decompression, without real-time electromyography monitoring. Posterior screws were used in all patients. Visual analog scale (VAS) score and Oswestry Disability Index (ODI) were evaluated before and 6 months after surgery. Surgical complications were also evaluated. RESULTS: Pain scores significantly improved after surgery, compared to those before surgery (p<0.05). There was no patient who underwent revision surgery. There was no spinal nerve, major vessel, peritoneal, or urinary injury. Few patients showed symptoms from psoas invasion. CONCLUSION: OLIF surgery produced good surgical results without any major complication.
Adult ; Aged ; Decompression, Surgical/*methods ; Electromyography ; Female ; Humans ; Lumbar Vertebrae/surgery ; Male ; Middle Aged ; Pain ; Pain Measurement ; Scoliosis/*surgery ; Spinal Diseases/surgery ; Spinal Fusion/*methods ; Spondylolisthesis/*surgery ; Treatment Outcome ; Young Adult

STUDY DESIGN: Experimental animal study. PURPOSE: To evaluate pain-related behavior and changes in nuclear factor-kappa B (NF-kB), receptor activator of NF-kB (RANK), and ligand (RANKL) in dorsal root ganglia (DRG) after combined sciatic nerve compression and nucleus pulposus (NP) application in rats. OVERVIEW OF LITERATURE: The pathological mechanisms underlying pain from lumbar-disc herniation have not been fully elucidated. RANKL are transcriptional regulators of inflammatory cytokines. Our aim was to evaluate pain-related behavior and RANKL expression in DRG after sciatic-nerve compression and application of NP in rats. METHODS: Mechanical hyperalgesia and RANKL expression were assessed in three groups of rats: NP+sciatic nerve compression (2 seconds), sham-operated, and controls (n=20 each). Mechanical hyperalgesia was measured every other day for 3 weeks using von Frey filaments. RANKL expression in L5 DRGs was examined at five and ten days after surgery using immunohistochemistry. RESULTS: Mechanical hyperalgesia was observed over the 12-day observation period in the NP+nerve compression group, but not in the control and sham-operated animal groups (p<0.05). RANKL immunoreactivity was seen in the nuclei of L5 DRG neurons, and its expression was significantly upregulated in NP+nerve compression rats compared with control and sham-operated rats (p<0.01). CONCLUSIONS: The exposure of sciatic nerves to mechanical compression and NP produces pain-related behavior and up-regulation of RANKL in DRG neurons. RANKL may play an important role in mediating pain after sciatic nerve injury with exposure to NP.
Animals ; Cytokines ; Diagnosis-Related Groups ; Ganglia, Spinal* ; Hyperalgesia ; Immunohistochemistry ; Negotiating ; Neurons ; NF-kappa B ; RANK Ligand* ; Rats* ; Sciatic Nerve* ; Up-Regulation

STUDY DESIGN: Experimental animal study. PURPOSE: To evaluate pain-related behavior and changes in glial activity in the spinal dorsal horn after combined sciatic nerve compression and nucleus pulposus (NP) application in rats. OVERVIEW OF LITERATURE: Mechanical compression and inflammation caused by prostaglandins and cytokines at disc herniation sites induce pain. Structural changes and pain-associated cytokines in the dorsal root ganglia and spinal dorsal horn contribute to prolonged pain. Glial cells in the spinal dorsal horn may also function in pain transmission. METHODS: The sciatic nerve was compressed with NP for 2 seconds using forceps in the NP+nerve compression group; the sham-operated group received neither compression nor NP; and the control group received no operation. Mechanical hyperalgesia was measured for 3 weeks using von Frey filaments. Glial activity in the spinal dorsal horn was examined 7 days and 14 days postsurgery using anti-glial fibrillary acidic protein and anti-Ionized calcium binding adaptor molecule-1 antibodies to detect astrocytes and microglia, respectively. RESULTS: Mechanical hyperalgesia was detected throughout the 14-day observation in the NP+nerve compression group, but not in control or sham-operated groups (p<0.05). Both astrocytes and microglia were significantly increased in the spinal dorsal horn of the NP+nerve compression group compared to control and sham groups on days 7 and 14 (p<0.05). CONCLUSIONS: Nerve compression with NP application produces pain-related behavior, and up-regulates astrocytes and microglia in the spinal dorsal horn, suggesting that these glia may be related to pain transmission.
Animals ; Antibodies ; Astrocytes ; Calcium ; Cytokines ; Ganglia, Spinal ; Horns ; Hyperalgesia ; Inflammation ; Microglia ; Neuroglia ; Prostaglandins ; Rats* ; Sciatic Nerve* ; Spinal Cord* ; Surgical Instruments ; Up-Regulation*

STUDY DESIGN: Retrospective case series. PURPOSE: To classify back muscle degeneration using magnetic resonance imaging (MRI) and investigate its relationship with back pain after surgery. OVERVIEW OF LITERATURE: Back muscle injury and degeneration often occurs after posterior lumbar surgery, and the degeneration may be a cause of back pain. However, the relationship between back muscle degeneration and back pain remains controversial. METHODS: A total of 84 patients (average age, 65.1 years; 38 men, 46 women) with lumbar spinal stenosis underwent posterior decompression surgery alone. MRI (1.5 tesla) was evaluated before and more than a year after surgery in all patients. Muscle on MRI was classified into three categories: low intensity in T1-weighted imaging, high intensity in T2-weighted imaging (type 1), high intensity in both T1- and T2-weighted images (type 2), and low intensity in both T1- and T2-weighted imaging (type 3). The prevalence of the types and their relationship with back pain (determined on a visual analog scale) were evaluated. RESULTS: MRI revealed muscle degeneration in all patients after surgery (type 1, 6%; type 2, 82%; and type 3, 12%). Type 2 was significantly more frequent compared with types 1 and 3 (p<0.01). Low back pain was significantly improved after surgery (p<0.01). Low back pain was not associated with any MRI type of muscle degeneration after surgery (p>0.05). CONCLUSIONS: Various pathologies of back muscle degeneration after posterior lumbar surgery were revealed. Type 2 (fatty) change was most frequent, and other patients had type 3 (scar) or type 1 (inflammation or water-like) changes. According to the Modic classification of bone marrow changes, Modic type 1 change is associated with inflammation and back pain. However, no particular type of back muscle degeneration was correlated with back pain after surgery.
Back Muscles* ; Back Pain ; Bone Marrow ; Classification* ; Decompression ; Humans ; Inflammation ; Low Back Pain* ; Magnetic Resonance Imaging ; Male ; Pathology ; Prevalence ; Retrospective Studies ; Spinal Stenosis

STUDY DESIGN: Retrospective case series. PURPOSE: To classify back muscle degeneration using magnetic resonance imaging (MRI) and investigate its relationship with back pain after surgery. OVERVIEW OF LITERATURE: Back muscle injury and degeneration often occurs after posterior lumbar surgery, and the degeneration may be a cause of back pain. However, the relationship between back muscle degeneration and back pain remains controversial. METHODS: A total of 84 patients (average age, 65.1 years; 38 men, 46 women) with lumbar spinal stenosis underwent posterior decompression surgery alone. MRI (1.5 tesla) was evaluated before and more than a year after surgery in all patients. Muscle on MRI was classified into three categories: low intensity in T1-weighted imaging, high intensity in T2-weighted imaging (type 1), high intensity in both T1- and T2-weighted images (type 2), and low intensity in both T1- and T2-weighted imaging (type 3). The prevalence of the types and their relationship with back pain (determined on a visual analog scale) were evaluated. RESULTS: MRI revealed muscle degeneration in all patients after surgery (type 1, 6%; type 2, 82%; and type 3, 12%). Type 2 was significantly more frequent compared with types 1 and 3 (p<0.01). Low back pain was significantly improved after surgery (p<0.01). Low back pain was not associated with any MRI type of muscle degeneration after surgery (p>0.05). CONCLUSIONS: Various pathologies of back muscle degeneration after posterior lumbar surgery were revealed. Type 2 (fatty) change was most frequent, and other patients had type 3 (scar) or type 1 (inflammation or water-like) changes. According to the Modic classification of bone marrow changes, Modic type 1 change is associated with inflammation and back pain. However, no particular type of back muscle degeneration was correlated with back pain after surgery.
Back Muscles* ; Back Pain ; Bone Marrow ; Classification* ; Decompression ; Humans ; Inflammation ; Low Back Pain* ; Magnetic Resonance Imaging ; Male ; Pathology ; Prevalence ; Retrospective Studies ; Spinal Stenosis

PURPOSE: Sacroiliac fixation using iliac screws for highly unstable lumbar spine has been reported with an improved fusion rate and clinical results. On the other hand, there is a potential for clinical problems related to iliac fixation, including late sacroiliac joint arthritis and pain. MATERIALS AND METHODS: Twenty patients were evaluated. Degenerative scoliosis was diagnosed in 7 patients, failed back syndrome in 6 patients, destructive spondyloarthropathy in 4 patients, and Charcot spine in 3 patients. All patients underwent posterolateral fusion surgery incorporating lumbar, S1 and iliac screws. We evaluated the pain scores, bone union, and degeneration of sacroiliac joints by X-ray imaging and computed tomography before and 3 years after surgery. For evaluation of low back and buttock pain from sacroiliac joints 3 years after surgery, lidocaine was administered in order to examine pain relief thereafter. RESULTS: Pain scores significantly improved after surgery. All patients showed bone union at final follow-up. Degeneration of sacroiliac joints was not seen in the 20 patients 3 years after surgery. Patients showed slight low back and buttock pain 3 years after surgery. However, not all patients showed relief of the low back and buttock pain after injection of lidocaine into the sacroiliac joint, indicating that their pain did not originate from sacroiliac joints. CONCLUSION: The fusion rate and clinical results were excellent. Also, degeneration and pain from sacroiliac joints were not seen within 3 years after surgery. We recommend sacroiliac fixation using iliac screws for highly unstable lumbar spine.
Aged ; Arthritis/*surgery ; Bone Screws ; Female ; Humans ; Low Back Pain/diagnosis/epidemiology ; Lumbar Vertebrae/*surgery ; Male ; Middle Aged ; Pain/diagnosis/*epidemiology ; Sacroiliac Joint/*immunology/*pathology

PURPOSE: Chronic low back pain is a common clinical problem. As medication, non-steroidal anti-inflammatory drugs are generally used; however, they are sometimes non-effective. Recently, opioids have been used for the treatment of chronic low back pain, and since 2010, transdermal fentanyl has been used to treat chronic non-cancer pain in Japan. The purpose of the current study was to examine the efficacy of transdermal fentanyl in the treatment of chronic low back pain. MATERIALS AND METHODS: This study included patients (n=62) that suffered from chronic low back pain and were non-responsive to non-steroidal anti-inflammatory drugs. Their conditions consisted of non-specific low back pain, multiple back operations, and specific low back pain awaiting surgery. Patients were given transdermal fentanyl for chronic low back pain. Scores of the visual analogue scale and the Oswestry Disability Index, as well as adverse events were evaluated before and after therapy. RESULTS: Overall, visual analogue scale scores and Oswestry Disability Index scores improved significantly after treatment. Transdermal fentanyl (12.5 to 50 microg/h) was effective in reducing low back pain in 45 of 62 patients; however, it was not effective in 17 patients. Patients who experienced the most improvement were those with specific low back pain awaiting surgery. Adverse events were seen in 40% of patients (constipation, 29%; nausea, 24%; itching, 24%). CONCLUSION: Disability Index scores in 73% of patients, especially those with specific low back pain awaiting surgery; however, it did not decrease pain in 27% of patients, including patients with non-specific low back pain or multiple back operations.
Administration, Cutaneous ; Adult ; Aged ; Aged, 80 and over ; Chronic Disease ; Female ; Fentanyl/*administration & dosage/*therapeutic use ; Humans ; Low Back Pain/*drug therapy ; Male ; Middle Aged ; Young Adult