The effect of repeated strontium-89 chloride therapy on bone pain palliation in patients with skeletal cancer metastases

One hundred and eighteen patients with painful skeletal metastases of malignant diseases (predominantly prostate, breast and lung cancer) were treated with 150 MBq of strontium-89 chloride (Metastron, Amersham, UK) intravenously. The results were evaluated according to a score considering pain relief, mobility, analgesic intake and general feeling. In only five patients (4.2%) was no improvement observed; mild improvement was noted in 48 (40.7%), and substantial or complete improvement in 56 (47.5%) and 9 (7.6%), respectively. The mean painless period after a single 89SrCl dose was 3.3 +/- 2.28 months (in patients with prostate, lung, breast and other types of cancer it was 3.65 +/- 2.11, 3.29 +/- 1.27, 3.08 +/- 0.48 and 3.44 +/- 1.36 months, respectively). During a 3-year study, 89SrCl treatment was successively repeated up to 5 times in some patients (total number of Metastron applications was 256) who benefited from the first Metastron administration and did not show signs of myelosuppression. Even after repeated treatment, relief was consistent and the duration of the period without pain increased (in particular in patients with breast cancer, in whom the period of relief was prolonged from 3.08 +/- 0.48 months after the first dose to 5.33 +/- 2.36 months after the fifth 89SrCl administration). The increased painless period was not observed after repeated treatment in the patient group comprising miscellaneous types of cancer, and the degree of improvement was less apparent. During the course of successive 89SrCl treatments, transient signs of myelosuppression indicated by a decrease in white cell and thrombocyte counts of at least 25% were observed 10 times after Metastron administration (twice in two patients), i.e. in 3.9% of all 89SrCl administrations; these transient haematological changes of moderate grade were closely connected with Metastron administration. Palliative treatment of metastatic skeletal pain with 89SrCl improves the quality of life in most patients suffering from prostate, lung and breast cancer and may be safely repeated with the same benefit and without significant myelosuppression. The beneficial effect of 89SrCl treatment seems to be less pronounced in other types of cancer with painful skeletal metastases.     

Platinum compounds as radiosensitizers in strontium-89 metabolic radiotherapy

PURPOSE: Strontium-89 is currently used for the treatment of painful bone metastases. This study reports on two preliminary experiences with low-dose platinum compounds, carboplatin and cisplatin, as radiosensitizers in 89Sr therapy. PATIENTS AND METHODS: 30 patients entered the carboplatin study: 15 patients (Group A) were treated with 148 MBq 89Sr followed by carboplatin (100 mg/m2 at 7 and 21 days) and 15 patients (Group B) were treated with 89Sr alone. 12 patients entered the cisplatin study: six patients (Arm 1) received 148 Mq 89Sr plus cisplatin (50 mg/m2) in two administrations (immediately before and 10 days after 89Sr injection) and six patients (Arm 2) received 89Sr plus two placebo administrations. Pain response was assessed 8 weeks after the therapy on the Wisconsin score modifications. RESULTS: No clinically significant adverse effects or myelosuppression by platinum compounds were observed. In carboplatin study a pain response was observed in 20 of 27 (74%) evaluable patients, 13/15 in group A and 7/12 in group B. The pain response in the patients treated with 89Sr and carboplatin was clearly superior to that seen in the patients treated with 89Sr alone (P = 0.025), whereas survival was only marginally better in the combined treatment group (8.1 vs 5.7 months, P = 0.19). In cisplatin study a pain response was observed in 10 of 12 (83%) evaluable patients, 5/6 in Arm 1 and 4/6 in Arm 2. CONCLUSIONS: Low-dose platinum compounds seem to enhance the effects of 89Sr radioisotope therapy on pain from bone metastases without relevant hematological toxicity.     

Radiation therapy in the management of symptomatic bone metastases: the effect of total dose and histology on pain relief and response duration

PURPOSE: In order to better define variables and factors that may influence the pain response to radiation, and to look for a radiation regimen that can assure the highest percentage and the longest duration of pain relief, we performed a prospective, although not randomized, study on patients with bone metastases from various primary sites. METHODS AND MATERIALS: From December 1988 to March 1994, 205 patients with a total of 255 solitary or multiple bone metastases from several primary tumors were treated in our radiotherapy center with palliative intent. Irradiation fields were treated with three main fractionation schedules: (1) Conventional fractionation: 40-46 Gy/20-23 fractions in 5-5.5 weeks; (2) Short course: 30-36 Gy/10-12 fractions in 2-2.3 weeks; (3) Fast course: 8-28 Gy/1-4 consecutive fractions. Pain intensity was self-assessed by patients using a visual analogic scale graduated from 0 (no pain) to 10 (the strongest pain one can experience). Analgesic requirement was assessed by using a five-point scale, scoring both analgesic strength and frequency (0 = no drug or occasional nonopioids; 1 = Nonopioids once daily; 2 = Nonopioids more than once daily; 3 = Mild opioids (oral codeine, pentazocine, etc.), once daily; 4 = Mild opioids more than once daily; 5 = Strong opioids (morphine, meperidine, etc.). Complete pain relief meant the achievement of a score < or = 2 in the pain scale or 0 in the analgesic requirement scale. Partial pain relief indicated a score of 3 to 4 or of 1 to 2 on the former and latter scale, respectively. RESULTS: Total pain relief (complete + partial) was observed in 195 (76%) sites, in 158 of which (62%) a complete response was obtained. Metastases from NSC lung tumors appeared to be the least responsive among all primary tumors, with 46% complete pain relief in comparison to 65% and 83% complete relief in breast (p = 0.04) and in prostate metastases (p = 0.002), respectively. A significant difference in pain relief was detected among the several ranges of total dose delivered to the painful metastases, with 81%, 65%, and 46% complete relief rates in the 40-46 Gy, 30-36 Gy (p = 0.03), and 8-28 Gy (p = 0.0001) dose ranges respectively. A straight correlation between total dose and complete pain relief was confirmed by the curve calculated by the logistic model which shows that doses of 30 Gy or more are necessary to achieve complete pain relief in 70% or more of bone metastases. This correlation holds also for the duration of pain control, as shown by the actuarial analysis of time to pain progression. Multivariate analyses, with complete pain relief and time to pain progression as endpoints show a highly significant effect of radiation dose (p = 0.0007) and performance status (p = 0.003), with lower rates of complete pain relief and shorter time to pain progression observed after smaller radiation total doses or higher Eastern Cooperative Oncology Group (ECOG) scores. CONCLUSION: Although single-dose or short course irradiation is an attractive treatment in reducing the number of multiple visits to radiotherapy departments for patients with painful bone metastases, it is nevertheless clear that aggressive protracted treatments seem to offer significant advantages especially for patients in whom the expected life span is not short.     

Combination chemotherapy with cis-platinum and ifosfamide for hormone unresponsive prostate cancer

PURPOSE: There is no effective therapy against hormone refractory prostate cancer. This led us to evaluate the effectiveness and toxicity of cis-platinum (CDDP) and ifosfamide (IFM) combination chemotherapy in the patients with hormone-unresponsive carcinoma of the prostate. METHODS: Patients with hormone-unresponsive prostate cancer were scheduled to receive CDDP 70 mg/m2 intravenously on day 1 and IFM 1.2 g/m2/day intravenously on day 1 through day 5 of 28-day cycle. RESULTS: Twenty seven patients with hormone unresponsive prostate cancer were enrolled onto this trial. Of these patients, seven (26%) demonstrated a partial objective response (PR), and ten (37%) a stable disease (ST). The response duration of PR cases lasted from 6 to 49 months with a median of 16 months and the response duration of PR + ST cases lasted from 3 to 36 months with a median of 10 months. Subjective improvement was obtained in 11 patients (41%). Survival duration of all cases were 4 to 89 months with a median of 23 months and probabilities of survival at 3 years and 5 years were 36% and 24%, respectively. The toxicity of this treatment was mostly mild to moderate, anemia (96%), leukocytopenia (89%), anorexia (81%), alopecia (67%), thrombocytopenia (44%), hematuria (38%), renal dysfunction (19%) and liver dysfunction (7%) were noticed. Severe toxicity was observed in two cases, one acute renal failure and one endotoxin shock. CONCLUSION: We conclude that CDDP and IFM combination chemotherapy was active regimen for hormone unresponsive prostate cancer.     

Pamidronate infusions as single-agent therapy for bone metastases: a phase II trial in patients with breast cancer

Pamidronate is a potent biphosphonate which modulates tumour-induced osteolysis (TIO) by inhibiting osteoclast-mediated bone resorption. In a phase II trial, 69 breast cancer patients with symptomatic progressive bone metastases were given infusions of pamidronate 60 mg over 1 or 4 h every 2 weeks for a maximum of 13 infusions or until progressive disease (PD) at any site. No other systemic anticancer therapy was allowed. Pain was measured using a visual analogue scale, mobility using a detailed eight-point questionnaire and analgesic intake using a six-point scale. Improvements in pain, mobility and analgesic scores occurred in 61, 50 and 30% of patients, respectively, with 33, 21 and 16% achieving a 40% improvement for > or = 8 weeks. At trial discontinuation, baseline levels of pain and mobility had improved by 27% (P = 0.001) and 20% (P = 0.004), respectively, despite a one category reduction in analgesic intake in 27% of patients. Using this relatively high dose of pamidronate, symptomatic response was independent of the number of bone metastases and also of infusion rate. The infusions were well tolerated with no major toxicities reported. Pamidronate infusions provide useful palliation for breast cancer patients with symptomatic bone metastases.     

Giant cranial base tumours

Thirty-three patients with giant (diameter > or = 4.5 cm) cranial base tumours who underwent surgery at the Hadassah Hospital over the last ten years are described. Twenty-three of the patients had meningiomas, 4 neurinomas, one giant cell tumour, one haemangiopericytoma, and 4 had malignant meningiomas. Four tumours were at the cerebellopontine angle, 9 within the anterior cranial fossa, 8 petroclival, 8 on middle fossa floor, and 4 along the sphenoid ridge. The average pre-operative symptom duration was 31 months, range 3-180 months. Nineteen patients had a radical tumour resection, 10 subtotal, and 4 a partial resection on an average 1.7 operations per patient. The mean follow-up period from the first operation was 39 months (range 2-120). There was no mortality peri-operatively or during the follow-up period. The mean pre-operative Karnofsky score was 68 and at the last follow-up 76. There was no correlation between histology and degree of resection, complications, or status at last follow-up. The best resections (92% radical) and outcome (mean Karnofsky 92) with the least number of operations (mean 1.4) were in the anterior fossa and along the sphenoid wing. The patients requiring the most operations (mean 2.1), having the smallest percentage of radical resections (25%) and the least favourable outcomes (mean Karnofsky 52) were those with petroclival tumours. Patients with giant cranial base tumours have a good overall long-term prognosis, but especially those with petroclival tumours challenge us to improve our techniques.     

An evaluation of the influence of devazepide and CCK-8S on the intact and resected rat liver

BACKGROUND: Chest wall recurrence of breast cancer after mastectomy, radiation therapy, and chemotherapy poses a therapeutic dilemma. Further intervention with any or all of these modalities is often futile and morbid. Left untreated, severe pain, infection, and suffering occur. OBJECTIVE: To ascertain whether photodynamic therapy may present a palliative option for these individuals. METHODS: A total of 86 lesions (2.4-cm mean diameter) were treated on eight patients who had biopsy-proven chest wall recurrence despite surgery, chemotherapy, and radiation therapy. Each patient underwent a single photodynamic therapy session in which 1.2 mg/kg of the drug tin ethyl etiopurpurin (Purlytin) was injected and followed 24 hours later by laser light treatment at 660 +/- 3 nm (at 150 mW/cm2 for a total light dose of 200 J/cm2). RESULTS: With a minimum 6-month follow-up, the objective response rates after photodynamic therapy were complete response, 92%; partial response, 8%; and no response, 0%. Lesions less than 0.5 cm had a 100% complete response. Morbidity was minimal with no systemic toxicity. One patient had a wound infection that responded to oral antibiotics. No photosensitivity reactions were reported in this set of patients. Posttreatment pain was reported and could be treated with medication and application of cold compresses. CONCLUSIONS: Photodynamic therapy offers an excellent local control rate of chest wall recurrence with minimal morbidity after multimodality treatment failure. The treatment is given in a single session and on an outpatient basis. In patients who may register a partial response or have recurrence or the incidence of further chest wall nodules after photodynamic therapy, the treatment is repeatable.     

Long-term follow up of dorsal root entry zone lesions in brachial plexus avulsion

The long-term results of 44 patients who underwent dorsal route entry zone (DREZ) lesioning for pain secondary to brachial plexus avulsion are reported with a mean clinical follow up period of 63 months. The postoperative analgesic effect was judged by the patients as being good (greater than 75% pain reduction), fair (25-75% pain reduction), or poor (0-25% pain reduction). With these criteria 35 patients (77%) had continuing good (30 cases, 68%) or fair (five cases, 11%) pain relief at the time of final follow up. Eight cases (18%) had persisting neurological deficits, although these were generally mild. DREZ thermocoagulation is an effective procedure for relieving deafferentation pain. The analgesic effect which is produced in the early postoperative period seems to be maintained in the long-term.     

Treatment of severe hypertriglyceridemia lowers plasma viscosity

PURPOSE: To assess the rate and duration of response to palliative radiotherapy (RT) in patients with metastatic melanoma or renal cell carcinoma. PATIENTS AND METHODS: From 1992 to 1995, 90 patients were entered into a nonrandomized study. Goals of palliative RT were prospectively defined and subjective response was documented at the end of RT, after 2-6 weeks, and every 3 months thereafter. Most patients were treated with 5 x 4 Gy or 10 x 3 Gy. RESULTS: Relief of pain from bone lesions was observed in 26 of 40 cases, with a duration of response of 2.4 months, corresponding to 57% of the remaining lifetime. A total of 55% of patients with persistent neurologic dysfunction despite corticosteroids improved, for a duration of 2.5 months (86% of the further lifespan). Freedom from symptoms in patients treated for impending neurological complications from metastases to the brain, spine, or nerve plexus was documented for 86-100% of their lifetime. CONCLUSIONS: Despite the methodological flaws discussed, the efficacy of a short course of palliative RT for so-called radioresistant tumors is demonstrated.     

Inhibitors of tyrosine kinase

BACKGROUND AND OBJECTIVES: Neurolytic superior hypogastric plexus block has been shown to be safe and effective in selected cancer patients. A large cohort of patients was studied to evaluate the continued efficacy and safety of this block in cancer patients with advanced disease. METHODS: A total of 227 pelvic pain patients with gynecological, colorectal, or genitourinary cancer who experienced poor pain control due to either progression of disease or to untoward side effects were enrolled in this study during a 3-year period. All pain patients receiving oral opioids were eligible to participate. A bilateral percutaneous neurolytic superior hypogastric plexus block with 10% phenol was performed 1 day after a successful diagnostic block with 0.25% bupivacaine. RESULTS: All patients reported a visual analog scale (VAS) pain score of 7-10/10 before the block. A positive response to a diagnostic block was obtained in 159 patients (79%). Overall, 115 patients of the 159 patients who responded to a diagnostic block (72%, 95% confidence interval of 65-79%) had satisfactory pain relief (VAS < 4/10), 99 (62%) after one block, and 16 (10%) after a second block. The remaining 44 patients (28%) had moderate pain control (VAS 4-7/10) after two blocks and received oral pharmacological therapy and epidural analgesic therapy with good results. Both groups experienced significant reductions in oral opioid therapy after the neurolytic blocks. No additional blocks were required by patients who had a good response during a follow-up period of 3 months. No complications related to the block were detected. CONCLUSIONS: Neurolytic superior hypogastric plexus block provided both effective pain relief and a significant reduction in opioid usage (43%) in 72% of the patients who received a neurolytic block. Overall, this represents 51% of the patients enrolled in the study. Poor results should be expected in patients with extensive retroperitoneal disease overlying the plexus because of inadequate spread of the neurolytic agent.     

Pathogenesis of porcine Actinobacillus pleuropneumonia: Part I. Effects of surface components of Actinobacillus pleuropneumoniae in vitro and in vivo

The aim of this study was to evaluate the quality of pain management in prehospital emergency care and to get more information about the administration of analgesics in prehospital patients. METHODS: Patients with painful diseases or injuries who had been brought to Munich hospital's were included in the study. Immediately after having reached the hospitals' emergency department, they were evaluated using a 101-point visual analogue scale for the severity of pain at four predefined periods. Information about the patient, the diagnosis, and the analgesic treatment used by the emergency teams were drawn from the patient's chart. RESULTS: A total of 462 patients were included in the study. The mean pain score on arrival of the emergency team was 64 points; 36.5% of the patients were treated with analgesics. In 28.1% the emergency team tried to reduce pain through external measures (i.e., setting of fractures). In 35.3% there was no therapeutic intervention. In cases in which analgesic therapy was initiated, a definite reduction in pain was achieved during emergency care. Visual analogue scores decreased from 70 points at the beginning to 29 points at arrival to the hospital's emergency department. Analgesics were most frequently used for patients with cardiopulmonary diseases (47.2%), followed by patients with traumatic accidents (35.5%) and patients with acute abdominal pain (25.2%). Of the analgesics, opioids were given most frequently (87.0%). Nonopioid analgesic agents were used in 32.1%. The results of our investigation demonstrate that in many cases the administration of analgesics is not individualized to the patients needs. CONCLUSION: During the prehospital period of emergency care many patients suffer from severe pain. The development of patient-oriented concepts concerning pain management could contribute to improvement of pain therapy in prehospital emergency medicine.     

An unprocessed pseudogene of inducible nitric oxide synthase gene in human

Over 4.5 years, 32 patients with spinal epidural metastases were decompressed and stabilized. Median survival was 9.5 months. Myelopathy was the predominant indication (41%) for the operation, intractable pain (microinstability) the second most important. The type of tumor spreading and biomechanics necessitated ventral decompression and stabilization in 65%. Corporectomy or extensive laminectomy was always combined with internal fixation and bone cement. With the exception of six patients (5 early deaths), all patients were able to walk after surgery. The Karnofsky index was improved significantly from 35 to 66%. The longest survival time was found in breast carcinomas and myelomas. Preoperative radiological embolization was a keystone in the treatment. Indication for surgery in spinal metastases is critical and needs an interdisciplinary approach. When the patient is suffering from higher degrees of paresis or even paralysis, he/she is no longer an ideal candidate for the operation. The same applies in the presence of uncontrolled primary tumors and neoplastic disease of the GI tract and the bronchus.     

Mitochondrial transmembrane potential and free radical production in excitotoxic neurodegeneration

OBJECTIVE: To evaluate quality-of-life (QOL) parameters in patients undergoing esophagectomy, curative or palliative, for carcinoma. DESIGN: Nonconsecutive case series. PATIENTS: Eighty-eight patients who underwent esophagectomy for cancer (curative, n=49 [56%]; palliative, n=39 [44%]) provided QOL assessments over an 18-month period. SETTING: Procedures for referral care were performed by a single team of clinicians in a tertiary referral center. Evaluations of QOL were made by 1 independent trained investigator. OUTCOME MEASURES: Data were documented by questionnaire at interview and parameters evaluated included an esophageal module for the type and quantity of food intake, severity of related symptoms on eating, Eastern Cooperative Oncology Groups (ECOG) performance status, sleep, pain, leisure activity, working capacity, outlook on life, general well-being, and support from family and friends. A summation of selected parameters was used to calculate a total score. RESULTS: Significant improvements were recorded in both the curative and palliative groups for at least 1 year following surgery in the type (P<.03) and quantity (P<.03) of food intake and severity of diet-related symptoms (P<.02), when compared with preoperative considerations. Findings were comparable between the groups with regard to dietary intake. Pain status and total scores were worse in the palliative group at 9 months postoperatively but no significant differences between the groups were evident at any time for sleep, leisure activity, and ECOG performance status. CONCLUSIONS: To our knowledge, there are no previous data regarding a comparison of QOL considerations in patients who have undergone either potentially curative or palliative esophagectomy for malignant disease. Data analysis revealed that palliative esophagectomy provided enhanced QOL with marked symptomatic benefits and enjoyment of daily living comparable to that observed following curative resection.     

"Salvage" transjugular intrahepatic portosystemic shunts: gastric fundal compared with esophageal variceal bleeding

PURPOSE: To determine the efficacy of definitive surgery and radiation in patients aged 70 years and older with supratentorial glioblastoma multiforme. METHODS AND MATERIALS: We selected elderly patients (> or = 70 years) who had primary treatment for glioblastoma multiforme at our tertiary care institution from 1977 through 1996. The study group (n = 102) included 58 patients treated with definitive radiation, 19 treated with palliative radiation, and 25 who received no radiation. To compare our results with published findings, we grouped our patients according to the applicable prognostic categories developed by the Radiation Therapy Oncology Group (RTOG): RTOG group IV (n = 6), V (n = 70), and VI (n = 26). Patients were retrospectively assigned to prognostic group IV, V, or VI based on age, performance status, extent of surgery, mental status, neurologic function, and radiation dose. Treatment included surgical resection and radiation (n = 49), biopsy alone (n = 25), and biopsy followed by radiation (n = 28). Patients were also stratified according to whether they were optimally treated (gross total or subtotal resection with postoperative definitive radiation) or suboptimally treated (biopsy, biopsy + radiation, surgery alone, or surgery + palliative radiation). Patients were considered to have a favorable prognosis (n = 39) if they were optimally treated and had a Karnofsky Performance Status (KPS) score of at least 70. RESULTS: The median survival for patients according to RTOG groups IV, V, and VI was 9.2, 6.6, and 3.1 months, respectively (log-rank, p < 0.0004). The median overall survival was 5.3 months. The definitive radiation group (n = 58) had a median survival of 7.3 months compared to 4.5 months in the palliative radiation group (n = 19) and 1.2 months in the biopsy-alone group (p < 0.0001). Optimally treated patients had a median survival of 7.4 months compared to 2.4 months in those suboptimally treated (p < 0.0001). The favorable prognosis group had an 8.4-month median survival compared to 2.4 months in the unfavorable group (p < 0.0001). On multivariate analysis, the KPS, RTOG group, favorable/unfavorable prognosis, and optimal treatment/suboptimal treatment were significant predictors of survival. CONCLUSION: Elderly patients with good performance status (> or = 70 KPS) when treated aggressively with maximal resection and definitive radiation had longer survival than those treated with palliative radiation and biopsy. Aggressive treatment in such patients should be considered.     

VAD or VMBCP in multiple myeloma refractory to or relapsing after cyclophosphamide-prednisone therapy (protocol MY 85)

263 patients (median age 65+/-10 years) with multiple myeloma were treated with cyclophosphamide-prednisone. Out of this cohort, 103 patients had progressive disease and were randomly assigned to either VAD (vincristine, doxorubicin, dexamethasone; 50 cases) or VMBCP (vincristine, BCNU, cyclophosphamide, melphalan and prednisone; 53 cases). There were no statistical differences between the two groups with the respect to clinical, biological and radiological parameters. There was no difference in survival between the VAD and VMBCP groups. The 4 months response rate was similar in the two groups (50% VAD, 56% VMBCP). With multivariate analysis for survival (Cox model), two factors had a statistically significant impact: Karnofsky index (> 60) and albuminaemia (< 34 g/l). With both Karnofsky index > 60 and albuminaemia > or = 34 g/l, the median survival was 29 months v 2 months with a Karnofsky index < or = 60 and albuminaemia < 34 g/l (P<0.05). In conclusion, VAD or VMBCP had similar activity for salvage treatment in MM refractory or relapsing to first-line treatment with cyclophosphamide-prednisone.     

The Graf stabilisation system: early results in 50 patients

The results of the first 50 consecutive patients using the Graf stabilisation system are presented. The average age of the patients was 41 years; there were 32 women and 18 men in the group. All patients suffered from intractable symptomatic degenerative disc disease which could be localised to one or more levels. All patients gave a history of chronic back pain, but the mean period of severe disability was 24 months. The mean preoperative disability score (Oswestry questionnaire) was 59%. The average period of follow-up was 24 months (range 19-36 months). At the latest review, the mean disability score was 31%. The clinical results were classified as "excellent" or "good" in 72% of patients, "fair" in 10%, "the same" in 16% and "worse" in 2%. All but three patients felt that surgery was worthwhile. The results have not deteriorated over the period of follow-up.     

Malignant bone pain

Bone pain is one of the most frequent causes of pain in patients with cancer, and the levels of metastases and bone pain are not directly correlated. Nociceptors in the periosteum are probably stimulated by halisteresis or by inflammatory oedema leading to an increase in the intraosseous pressure. Some authors believe that the nociceptors in bone are mediated via intraosseous mechanoreceptors in the bone-matrix. At a low pain level the initial treatment is acetylsalicylic acid, paracetamol or other nonsteroidal antiinflammatory drugs. At increasing pain level initial doses of oral opioids are added. In severe bone pain, where conventional therapy seems difficult, opioids are administered by invasive techniques. In localised bone pain palliative radiation is the first treatment of choice. Corticosteroids induce an analgetic effect indirectly by reducing the inflammatory oedema, inhibiting the synthesis of prostaglandins and may inhibit excitatory nerve fibres. Endocrine treatment, calcitonin and biophosphonates have shown a documented pain-relieving effect in patients with disseminated breast and prostate cancer. Chemotherapy has shown a pain-relieving effect in patients with disseminated breast cancer, surgical intervention is used in stabilizing osteolytic bones before or after a fracture ensuring a reasonable relief of pain.     

Isolation, inoculation to insect host, and molecular phylogeny of an entomogenous fungus Paecilomyces tenuipes

BACKGROUND: To improve the poor prognosis of patients with advanced incurable gastric cancer, intensive chemotherapy combined with radical surgery was used. PATIENTS AND METHODS: Thirty patients with incurable gastric cancer were treated with a combination of 5-fluorouracil (370 mg/m2) and leucovorin (30 mg/person), given intravenously for five consecutive days, followed by cisplatinum (70 mg/m2) and etoposide (70 mg/m2) on days 6 and 20, delivered through a catheter placed either in the aorta with its tip at the level of the ninth thoracic vertebra or in the celiac artery. This treatment (FLEP therapy) was repeated twice every 5 weeks. Radical or palliative surgery followed chemotherapy. RESULTS: The overall response rate to the chemotherapy was 50.0% (15 of 30 patients, 95% confidence limit 0.305-0.671). Nineteen patients (15 with a partial response, three showing no change, and one with progressive disease) underwent surgery. Of these, nine underwent curative surgery and 10 palliative surgery. The median survival time was 6.5 months overall, 12.7 months for responders, and 4.7 months for nonresponders. Long-term survivors were exclusively found among patients with distant lymph node metastasis treated by curative surgery (55.6% at 5 years). CONCLUSIONS: Favorable results of this small phase II study justify a phase III trial.     

Analgesic efficacy of ibuprofen alone and in combination with codeine or caffeine in post-surgical pain: a meta-analysis

OBJECTIVE: To estimate the analgesic effect of ibuprofen and to test whether codeine and caffeine enhance its effect on post-surgical pain. METHOD: Systematic overview of the literature and meta-analysis of published randomised, controlled trials. RESULTS: Ibuprofen is effective in dental pain, episiotomy pain and other post-operative pain. There is a dose response relationship over the range 50-400 mg. The difference in total pain-relief score relative to placebo was 19-31%. On average, patients were over three times more likely to obtain moderate to excellent pain relief with ibuprofen than with placebo (response-rate ratio = 3.45) and the number needed to treat was 2.44. Codeine 60 mg enhanced the analgesic effect of ibuprofen 400 mg by about 8% in the total pain-relief scale, but it also increased its adverse effects. The additive effect of caffeine was inconsistent. CONCLUSION: Ibuprofen is an effective analgesic in post-operative pain. Codeine 60 mg adds to the analgesic effect of ibuprofen 400 mg. Any additive caffeine effect requires validation.