Dorsal root ganglion pulsed radiofrequency for the management of intractable vertebral metastatic pain: a case series.

OBJECTIVE: Metastatic bone pain is characteristic of cancer pain and is a form of refractory cancer pain, as the pain includes not only nociceptive but also neuropathic pain. Although some drugs are effective in the management of painful bone metastases, pain while moving is one of the most refractory forms of pain. Although pulsed radiofrequency (RF) dramatically reduces neuropathic pain, chronic pain, and vertebral metastatic pain, the number of cases reported in these studies was very small (five or less). DESIGN: Case report. SETTING: Single pain center. PATIENTS: Fifteen patients suffering from intractable vertebral metastatic pain. INTERVENTIONS: Dorsal root ganglion (DRG) pulsed RF. OUTCOME MEASURES: A numerical rating scale (NRS) of pain at rest and while moving. RESULTS: Almost all patients experienced sound pain relief after the pulsed RF treatment. There were no severe side effects reported. CONCLUSION: DRG pulsed RF procedure provided sound pain relief for patients with intractable vertebral metastatic pain. Metastatic bone pain is characteristic of cancer pain and is a form of refractory cancer pain, as the pain includes not only nociceptive but also neuropathic pain. Although some drugs are effective in the management of painful bone metastases, pain while moving is one of the most refractory forms of pain. DRG pulsed RF procedure provided sound pain relief for patients with intractable vertebral metastatic pain.

Carbonyl reduction in the biosynthesis of a male sex pheromone secreted by the grape borer Xylotrechus pyrrhoderus.

Males of the cerambycid beetle Xylotrechus pyrrhoderus release a mixture of (S)-2-hydroxy-3-octanone [(S)-1] and (2S,3S)-2,3-octanediol [(2S,3S)-2] as a sex pheromone that attracts conspecific females. The chemical structures of these pheromone components include a common motif and are assumed to be biosynthetically related. Here, we show that deuterated (S)-1, applied on the cuticle of a pronotal pheromone gland, was converted into (2S,3S)-2, that included deuterium atoms, but a reverse conversion did not take place. These results reveal a carbonyl reductase to be active in the pheromone gland, and that the ketol is a biosynthetic precursor of the diol. Males did not produce (R)-1; however, deuterated (R)-1 was converted into (2R,3R)-2, indicating an attack of the enzyme from the opposite side of the hydroxyl group at the 2-position. Furthermore, to understand the substrate specificity of the enzyme, racemates of 2-hydroxy-3-hexanone and 2-hydroxy-3-decanone were synthesized and applied to the gland. Their conversion into the corresponding diols suggests that the enzyme reduces the carbonyl group at the 3-position, regardless of the chain length.

Combinations of low-dose antidepressants and low-dose pregabalin as useful adjuvants to opioids for intractable, painful bone metastases.

BACKGROUND: Systemic analgesics would not provide good enough pain relief for some kinds of cancer pain. Metastatic bone pain is characteristic of one of the refractory cancer pains, since the pain is not only nociceptive but also neuropathic. A low-dose antiepileptic-antidepressant combination with opioids is effective in the management of neuropathic cancer pain. OBJECTIVE: The aim was to see whether a low-dose antiepileptic-antidepressant combination is effective in the treatment of bone metastases. STUDY DESIGN: Randomized, controlled trial. SETTING: Pain Clinic in Japan. METHODS: Thirty-seven cancer patients, confirmed to have bone metastases, were allocated into 3 groups: P group took pregabalin 50 mg every 8 hours orally; P-I group took pregabalin 25 mg every 8 hours orally and imipramine 5 mg every 12 hours orally; P-M group took pregabalin 25 mg every 8 hours orally and mirtazapine 7.5 mg every 12 hours orally. Pain assessments were performed for 2 weeks. RESULTS: The total pain score significantly decreased in all 3 groups even one day after the start of the medication. The decreases in the P-I and P-M groups were significantly greater than those in the P group from Day 2. Also, the daily paroxysmal pain episodes significantly decreased in all 3 groups at Day one. The decreases in the P-M groups were significantly greater than those in the P group from Day one. The decreases in the P-I group were significantly greater than those in the P group from Day 3. CONCLUSION: Low-dose pregabalin-antidepressant combinations with opioids were effective in the management of painful bone metastases.

Neurolytic celiac plexus block reduces occurrence and duration of terminal delirium in patients with pancreatic cancer.

PURPOSE: WHO's three step ladder sometimes cannot provide adequate pain relief for pancreatic cancer. Some patients develop terminal delirium (TD). The aim of this study was to test if the addition of a celiac plexus block (CPB) to pharmacotherapy could reduce the incidence of TD. METHODS: Pancreatic cancer patients under the care of our palliative-care team were investigated with regard to the duration and occurrence of TD, pain scores [numerical rating score (NRS)] and daily opioid dose. Between August 2007 to September 2008, 17 patients received only pharmacotherapy (control group). Then, we modified our guideline for analgesia, performing CPB 7 days after the first intervention of our team. Between October 2008 to September 2009, 19 patients received CPB. RESULTS: The opioid doses in CPB group were significantly lower both at 10 days after the first intervention (3 days after CPB) (27 ± 11 vs. 66 ± 82 mg; p = 0.029) and 2 days before death (37 ± 25 vs. 124 ± 117 mg; p = 0.009). NRS in the CPB group were significantly lower both at 10 days after the first intervention (0 [0-2] vs. 3 [2-5], p < 0.0001) and 2 days before death (1 [0-2] vs. 3 [1-4.5], p = 0.018). The occurrence and duration of TD in CPB group were both reduced (42 vs. 94 %, p = 0.019; and 1.8 ± 2.9 vs. 10.4 ± 7.5 days, p = 0.0003). CONCLUSION: The duration and occurrence of TD and the pain severity were significantly less in pancreatic cancer patients who underwent neurolytic CPB.

Determination of doripenem penetration into human prostate tissue and assessment of dosing regimens for prostatitis based on site-specific pharmacokinetic-pharmacodynamic evaluation.

Prostatic hypertrophy patients prophylactically received a 0.5-hour infusion of doripenem (250 or 500 mg) before transurethral resection of the prostate. Doripenem concentrations in plasma and prostate tissue were measured chromatographically, and analysed pharmacokinetically using a three-compartment model. The approved doripenem regimens were assessed based on the time above the minimum inhibitory concentration for bacteria (T>MIC, % of 24 hours), an indicator for antibacterial effects, at the prostate. The prostate tissue/plasma ratios were 17.3% for the maximum drug concentration and 18.7% for the area under the drug concentration-time curve, and they were irrespective of the dose. Against Escherichia coli and Klebsiella species isolates, 500 mg once daily achieved a >90% probability of attaining the bacteriostatic target (20% T>MIC) in prostate tissue, and 500 mg twice daily achieved a >90% probability of attaining the bactericidal target (40% T>MIC) in prostate tissue.

Biosynthetic pathways of the sex pheromone components and substrate selectivity of the oxidation enzymes working in pheromone glands of the fall webworm, Hyphantria cunea.

The fall webworm, Hyphantria cunea Drury (Lepidoptera: Arctiidae), is a harmful polyphagous defoliator. Female moths produce the following four pheromone components in a ratio of about 5:4:10:2; (9Z,12Z)-9,12-octadecadienal (I), (9Z,12Z,15Z)-9,12,15-octadecatrienal (II), cis-9,10-epoxy-(3Z,6Z)-3,6-henicosadiene (III), and cis-9,10-epoxy-(3Z,6Z)-1,3,6-henicosatriene (IV). Although ¹³C-labeled linolenic acid was not converted into trienal II at the pheromone glands of H. cunea females, GC-MS analysis of an extract of the pheromone gland treated topically with ¹³C-labeled linolenyl alcohol showed the aldehyde incorporating the isotope. Other C18 and C19 fatty alcohols were also oxidized to the corresponding aldehydes in the pheromone gland, indicating a biosynthetic pathway of IIvia linolenyl alcohol and low substrate selectivity of the alcohol oxidase in the pheromone gland. On the other hand, epoxydiene III was expected to be produced by specific 9,10-epoxidation of the corresponding C21 trienyl hydrocarbon, which might be biosynthesized from dietary linolenic acid in oenocytes and transported to the pheromone gland. The final biosynthetic step in the pheromone gland was confirmed by an experiment using deuterated C21 triene, which was synthesized by the chain elongation of linolenic acid and LiAlD4 reduction as key reactions. When the labeled triene was administered to the female by topical application at the pheromone gland or injection into the abdomen, deuterated III was detected in a pheromone extract by GC-MS analysis. Furthermore, the substrate selectivity of epoxidase and selective incorporation by the pheromone glands were examined by treatments with mixtures of the deuterated precursor and other hydrocarbons such as C19-C23 trienyl, C21 dienyl, and C21 monoenyl hydrocarbons. The 9,10-epoxy derivative of each alkene was produced, while the epoxidation of the C21 monoene was poorer than those of the trienes and diene. The low selectivity indicated that the species-specific pheromone of the H. cunea female was mainly due to the critical formation of the precursor of each component.

Intravesical administration of pirarubicin against superficial bladder cancer: Relationship between tumor tissue concentration and exposure time in the bladder or therapeutic effect.

The aim of this study was to investigate the relationship between tissue concentrations and exposure times or therapeutic effect of an anthracycline anticancer drug, pirarubicin, in bladder cancer tissue after single intravesical administration against superficial bladder cancer. The concentrations of pirarubicin in tumor tissues and serum were measured at designated collection times after a single intravesical administration of pirarubicin (30 mg) in 22 patients with superficial bladder cancer. A wide range of concentrations of pirarubicin in bladder cancer tissue was observed (2.3-125 µg/g of tissue), although serum pirarubicin concentrations were not detected in any of the patients. Recurrence of superficial bladder cancer after transurethral resection of the bladder tumor (TUR-BT) was observed in 2 patients (9%). The concentration of pirarubicin in the tumor tissue tended to be higher as the exposure time increased. There was a weak relationship between the pirarubicin tissue concentration and tumor size. However, no significant relationship between tissue pirarubicin concentrations and the prophylactic effect against intravesical recurrence of bladder cancer after TUR-BT was observed. All patients had no adverse events, such as bladder irritation and local toxicity, caused by the treatment with pirarubicin. These findings suggest that prior to single intravesical administration of pirarubicin to patients with superficial bladder cancer the exposure time and tumor size should be considered.

Low-dose gabapentin as useful adjuvant to opioids for neuropathic cancer pain when combined with low-dose imipramine.

PURPOSE: Painful neuropathic conditions of cancer pain often show little response to nonopioid and opioid analgesics but may be eased by antidepressants and anticonvulsants. Although gabapentin is effective in the treatment of neuropathic pain in patients with cancer, some patients experience intolerable side effects sufficient to warrant discontinuation. The aim of this study was to see whether low-dose gabapentin is effective in treating cancer-related neuropathic pain when combined with low-dose imipramine. METHODS: Fifty-two cancer patients diagnosed as having neuropathic pain were allocated into four groups: G400-I group took gabapentin 200 mg and imipramine 10 mg every 12 h orally; G400 group took gabapentin 200 mg every 12 h orally; G800 group took gabapentin 400 mg every 12 h orally; I group took imipramine 10 mg every 12 h orally. RESULTS: Low-dose gabapentin-imipramine significantly decreased the total pain score and daily paroxysmal pain episodes. Several patients developed mild adverse symptoms in the four groups, and three patients discontinued treatment due to severe adverse events in the G800 group. CONCLUSION: Low-dose gabapentin-antidepressant combination with opioids was effective in managing neuropathic cancer pain without severe adverse effects.

Association between gefitinib and hemorrhagic cystitis and severely contracted bladder: a case report.

BACKGROUND: Gefitinib remains an excellent treatment option for patients with a variety of cancers, including non small cell lung cancer (NSCLC). However, clinicians must be aware of the potential of gefitinib to cause an inflammatory reaction in the skin, lungs and bladder. CASE PRESENTATION: We present a case on hemorrhagic cystitis and severely contracted bladder in a patient with NSCLC on gefitinib. CONCLUSIONS: Further studies are needed to substantiate the association of gefitinib therapy with hemorrhagic cystitis and contracted bladder.

The use of zoledronic acid in Japanese men with stage D2 prostate cancer.

Zoledronic acid (ZOL) is a new generation bisphosphonate with improved efficacy benefits over pamidronate in preclinical testing. In addition, ZOL is superior to pamidronate in the treatment of hypercalcemia of malignancy. ZOL is also the first bisphosphonate to demonstrate efficacy in patients with bone metastases from solid tumors other than breast cancer, such as prostate cancer. In this study, we investigated ZOL treatment in 17 Japanese men with advanced prostate cancer, treated at the Aichi Medical University Hospital between August 2006 and November 2007. The 17 patients had biopsy-confirmed prostate cancer and were found to harbor bone metastasis upon bone scintigraphy. ZOL was administered intravenously at a dose of 4 mg over 15 min every 4 weeks. ZOL was well tolerated with mild renal dysfunction in 2 patients (11.8%), while 1 patient (5.8%) developed skin rash. No significant side effects were observed. Subjective improvement in bone pain was reported in 14 patients (32.4%). ZOL, therefore, is a safe and effective drug that remains an important component of the urologist's armamentarium against advanced prostate cancer.

Cyclooxygenase-2 expression in invasive transitional cell carcinoma of the urinary bladder.

Cyclooxygenase-2 (COX-2) activity is reported to increase apoptosis, inhibit angiogenesis and reduce metastasis. We analyzed COX-2 expression in patients with invasive bladder cancer to evaluate the feasibility of selective COX-2 inhibitor treatment targeting COX-2. Forty patients with pathologically diagnosed invasive transitional cell carcinoma of the urinary bladder (pT2-pT4) were evaluated. Immunohistochemical staining was used to evaluate COX-2 expression, and cases with staining of ≥10% of tumor cells were defined as positive. In 2 patients, 0% of the primary tumors stained for COX-2, while 1-5% was stained in 16 patients, 5-10% in 3 patients and ≥10% in 19 patients (19/40, 47.5%). In terms of grade, 2 patients with grade 2 (2/3, 66.6%) and 17 patients with grade 3 (17/37, 45.4%) were COX-2 positive. When categorized by stage, 11 patients with pT2 (11/22, 50.0%), 6 with pT3 (6/13, 46.1%) and 2 with pT4 (2/5, 40.0%) were positive. Lymph node metastasis was observed in 10 patients; 2 of them, with pN2, were COX-2 positive. Those with COX-2-positive metastatic lymph nodes had grade 3 primary tumors, which were also COX-2 positive. In addition, COX-2-negative metastatic lymph node patients also had negative primary tumors. The results of this study suggest that 47.5% of patients with invasive bladder cancer may benefit from treatment with selective COX-2 inhibitors targeting COX-2, and that treatment efficacy can be expected in patients with lymph node metastasis when their primary tumors are COX-2 positive.