Strontium-89 for palliation of pain from bone metastases in patients with prostate and breast cancer

We have used strontium-89 chloride (89Sr) for the palliative treatment of metastatic bone pain. Seventy-six patients (50 males with prostate carcinoma and 26 females with breast cancer) were treated with 148 MBq of 89Sr. Sixteen patients were retreated, receiving two or three doses; the total number of injected doses was consequently 95. The Karnofsky performance status was assessed and pain and analgesia were scored on scales of 9 and 5 points, respectively. The efficacy of 89Sr was evaluated at 3 months of treatment. Three levels of response were considered: good - when there was an increase in the Karnofsky status and a decrease in the pain score (equal to or higher than 4) or analgesic score (equal to or higher than 1); partial - when there was an increase in the Karnofsky status and a decrease in the pain score (2 or 3 points) without significant changes in the analgesic score; no response - if no variation or deterioration in these parameters was observed. In prostate cancer patients, the response was good in 64% of cases and partial in 25%, and there was no response in the remaining 11%. In breast cancer patients, the response was good in 62% of cases and partial in 31%, and there was no response in the remaining 8%. Duration of the response ranged from 3 to 12 months (mean 6 months). In the patients who were retreated the effectiveness was as good as after the first dose of 89Sr. A decrease in the initial leucocyte and platelet counts was observed after the 1st month of treatment, with a gradual partial to complete recovery within 6 months. It is concluded that 89Sr is an effective agent in palliative therapy for metastatic bone pain in patients with prostate or breast carcinoma. If required, retreatment can be administered safely and with the same efficacy as is achieved by the first dose.     

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.     

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.     

Bisphosphonates for controlling pain from metastatic bone disease

The rationale for and efficacy of bisphosphonates for pain due to cancer that has metastasized to bone are reviewed. Typical strategies for controlling metastatic bone pain have consisted of opioids, nonsteroidal anti-inflammatory drugs, surgery to stabilize bone, cancer chemotherapy, radiation therapy, and radiopharmaceuticals. Cancer metastasis to bone can produce pain through the release of prostaglandins, bradykinin, substance P, and histamine; growth of tumor into surrounding tissue; stretching of the periosteum; and pathological fractures. It has been suggested that bisphosphonates can benefit these patients by decreasing the amount of pain or decreasing analgesic requirements. Bisphosphonates bind to hydroxyapatite crystals, making it more difficult for osteoclasts to recognize exposed unmineralized bone surfaces, and are directly toxic to osteoclasts. Etidronate disodium, pamidronate disodium, clodronate disodium, and alendronate sodium are bisphosphonates that have been studied in patients with painful bone metastases. Although each of these has shown at least some benefit, the most promising agent appears to be pamidronate, especially the i.v. formulation given monthly. Although oral formulations of this agent have been studied, poor bioavailability and adverse effects limit their usefulness. Adverse effects of bisphosphonates include GI reactions, impairment of renal function, anemia, and electrolyte abnormalities. Bisphosphonates are of some benefit in relieving metastatic bone pain, but the exact role, agent, route, and duration are issues that need further study.     

Sleep disorders. Overview and relationship to orofacial pain

Pain problems associated with the orofacial region need to be evaluated thoroughly. This article discusses the multiple approaches that may be necessary to gain the best result.     

Right ventricular bypass for palliation of cardiac sarcoma

A 33-year-old woman with a nonresectable right ventricular sarcoma and pulmonary outflow tract obstruction underwent a right ventricular bypass operation for symptomatic relief. The patient had an uneventful recovery and was asymptomatic on discharge, without jugular plethora or hepatomegaly. We consider this procedure to be an excellent palliative treatment of malignant right ventricular obstructive symptoms for improving the patient's quality of life.     

Choledochoduodenostomy for palliation in unresectable pancreatic cancer

Bcl-2 and bax are cellular proteins that are important in the regulation of apoptosis. Overexpression of bcl-2 protein is associated with prolonged cell survival, whereas overexpression of bax correlates with increased apoptosis after injury. It has been suggested that the ratio of bcl-2 and bax determines a cell's susceptibility to apoptosis. We studied bcl-2 and bax expression by immunohistochemical methods in 46 cases of B-cel non-Hodgkin's lymphoma characterized by the Revised European-American Lymphoma (REAL) classification to determine whether expression of these two proteins correlated with the histological subtype or the predicted clinical behavior (indolent v aggressive). For each case, both the percentage of cells staining as well as the intensity of staining of bcl-2 and bax were recorded, and a bcl-2-bax protein ratio (BBPR) was calculated. Bax staining was identified in 100% of the lymphomas studied. In contrast, bcl-2 staining was seen in only 67%. Bcl-2 expression correlated with the subtype of lymphoma with positive staining in 100% of small lymphocytic lymphomas, 80% of follicle center lymphomas, 38% of diffuse large cell lymphomas, 33% of high-grade B-cell Burkitt's-like lymphomas, 0% of Burkitt's lymphomas, and 0% of B-cell lymphoblastic lymphomas. The BBPR of indolent lymphomas (mean, 1.8) was significantly greater than the BBPR of aggressive lymphomas (mean, 0.6) (P < or = .002). This suggests that bax and bcl-2 expression may be linked to biological behavior in non-Hodgkin's B-cell lymphomas.     

Use of calcitonin in treatment of bone pain

The studies were carried out assessing the effect of calcitonin in the treatment of bone pain. In the years 1990-1992 43 patients were studied. Pain intensity scale was used with evaluation by doctor and patient.     

New study suggests radiation often underused for palliation

BACKGROUND: The exact pathogenic mechanism of the accumulation of subretinal fluid at the posterior pole of the fundus in cases of central serous chorioretinopathy (CSC) is not well established. Recently, it was reported that CSC is more frequent among patients with endogenous Cushing's syndrome. Thus, it has been suggested that glucocorticoids might be involved in the pathogenesis of CSC. Subsequently, additional observations, have confirmed the relationship between glucocorticoids and CSC. We present preliminary data on the endogenous cortisol secretion in patients with CSC. PATIENTS AND METHOD: Sixteen patients (14 men and 2 women, 35-65 years of age) suffering from CSC, not exposed to exogenous glucocorticoids and without clinical and/or biological stigmata of endogenous Cushing's syndrome, have been examined. Twenty four hour urinary free cortisol (24 h-UFC) secretion was measured within one week of their CSC episode. Twenty four hour urinary free cortisol of age and sex matched controls were also measured. RESULTS: Twenty four hour urinary free cortisol was 188.20 nmol/l +/- 34.1 for the patients suffering from CSC and 115.3 nmol/l +/- 63.4 for the control group (p < 0.05). CONCLUSION: These results give additional evidence that glucocorticoids may play a role in the pathogenesis of CSC. However, given the substantial variability of urinary free cortisol levels, as indicated by the increased SD, additional number of patients should be examined.     

Malignant bone pain: pathophysiology and treatment

2-acetyl aminofluorene (AAF) reacts in acidic conditions with nitrous fume yielding N-nitroso-AAF (N-NO-AAF), as previously described, that exerts more toxic and mutagenic effects than its parental compound. In this study, the effect of sodium nitrite (NaNO2) on the tumorigenicity of AAF in rats fed with AAF and NaNO2 was observed. Wistar rats were divided into five groups: group I served as control; group II were treated with NaNO2 (0.3%); group III was given 0.02% AAF alone; groups IV and V received both AAF and NaNO2 (0.2 and 0.3% respectively) in their diet for 12 weeks. At the end of the experiment, all rats in groups III, IV and V developed early stage phenomena of hepatocellular carcinoma, including hepatomegaly with variable-sized foci and neoplastic nodules. Severe damage was observed in the rats treated with AAF and NaNO2. Feeding of AAF (0.02%) for 3 months elevated the levels of c-Fos, c-Jun and c-Myc proteins in the rat livers. The AAF-induced c-Jun, c-Fos and c-Myc expressions were significantly magnified (P < 0.001) by NaNO2. These data confirmed that the strengthening of AAF-induced hepatocarcinogenesis by NaNO2 should be associated with its enhancing effect on the AAF-induced increases in the expressions of c-Jun, c-Fos and c-Myc.     

Application of rectal stents for palliation of obstructing rectosigmoid cancer

BACKGROUND: The rationale of palliative endoscopic treatment is to avoid a colostomy in patients with advanced disease and limited life expectancy. This study was conducted to evaluate the role of endoscopic stent implantation for palliation of obstructing rectal cancer. METHODS: Overall, 19 patients (aged 47-87 years) with nonresectable or metastatic rectal cancer were treated by stent insertion after laser recanalization or dilation. Three types of stents, i.e., plastic tubes (n = 8), self-expanding mesh stents (n = 6), and endocoil stents (n = 5), were used to maintain luminal patency. RESULTS: Endoscopic stent implantation was successfully performed in all 19 patients. Long-term luminal patency and satisfactory bowel function were achieved in 16 of 19 patients (84%). After a median follow-up of 6 months, eight of the patients have died and eight are still alive without evidence of recurrent obstruction. Dislocation of the endoprosthesis occurred in two of eight plastic tubes and one of five mesh stents. Recurrent obstruction due to tumor ingrowth was only observed in patients treated with self-expanding mesh stents (n = 2). In spite of reinsertion and laser therapy a colostomy was required in three of 19 patients. There was no evidence of treatment failure in five patients who received endocoil stents. None of the patients experienced serious complications related to the endoscopic procedure. CONCLUSIONS: Endoscopic stent implantation seems to be a safe and efficient palliative approach to selected patients with obstructing rectal cancer. Currently, self-expanding coil stents are superior to other devices because of lower risk of dislocation and tumor ingrowth.     

Causes and treatment of bone pain of malignant origin

Pain relief has been one of the oldest and most important duties of the physician. There has been little change with regard to this obligation of all caregivers. One-third of patients with advanced cancer will develop clinically relevant skeletal metastases and chronic pain during the course of their disease. All physicians involved in the treatment of cancer patients should know the basic principles of pain treatment. These are described in the following article with special regard to bone pain of malignant origin. Correct assessment of pain intensity and frequency, as well as of the probable causes of pain, and the administration of adequate analgesic treatment should achieve satisfactory results in the vast majority of patients. Every physician should obtain detailed knowledge of the indications and adequate administration of pain-killing therapy as well as possible adverse effects and their successful treatment. It is important in particular to concentrate on a few nonsteroidal anti-inflammatory drugs (NSAIDs) as well as opiates. Knowledge of adequate doses, maximal recommended daily doses, pharmacological properties, important adverse effects and interactions is essential for success in the daily routine. Only by selecting 2 or 3 drugs from each step in the analgesic ladder (WHO) will the nonspecialised physician obtain sufficient experience for optimal analgesia. Physicians should also not hesitate to contact other specialists (medical oncologists, radiotherapists, neurosurgeons, anaesthesiologists and others) in order to maximise benefit for an individual patient.     

The effect of bone drilling on pain in gonarthrosis

Problem doctors are a heterogeneous group, and it is sometimes difficult to determine whether a doctor is incompetent or simply makes repeated mistakes hard to avoid completely under pressure of the clinical work-load. The profession has a small repertoire of informal methods for dealing with situations where a colleague has become a problem. An interview study, carried out in Britain and Sweden, revealed the approaches most commonly used. It also showed that the problem doctor's colleagues often hesitate too long in taking the informal approach that the problem is much more difficult to resolve by the time department heads and administrators become involved.     

Self-expanding stents for the palliation of esophageal and gastric cardia cancer

Twenty-one endoscopic tube implantations were carried out in 24 patients with malignant stenosis of esophagus and gastric cardia using self-expanding metallic stents. The indications to endoscopic intubation were advanced stage of the tumor in 17 cases and risk factors which made resection inadvisable in 7 cases. In 3 patients it proved impossible to implant a stent endoscopically because the Authors were not able to pass the guide wire through the stenosis, while correct stent placement was achieved in 21 patients. Functional results were good in 18 patients, while 3 patients did not have any improvement of symptoms. Complications occurred in 9 patients (42.85%): 2 bleedings, 3 neoplastic obstructions, 1 food obstruction and 3 distal dislodgements of the prostheses were observed, but could readily be corrected. No death occurred. The median survival time was 151 days (range 25-545). This study suggests that endoscopic placement of metallic self-expanding stents is safe and has to be preferred to plastic stents for easier implantation and lower morbidity.     

Tissue localization of stable and radioactive nuclides by secondary-ion microscopy

Images of the distribution of a given nuclide in a section of biological tissue can be obtained at the microscopic level by "secondary-ion mass analysis." In this method, the images are formed by an ion-emission microscope wherein the specimen's atoms are progressively sputtered from the surface and the ions are selectively visualized by mass spectrometry according to their mass-to-charge ratios. Such images are obtained at the cost of the destruction of the specimen, which is progressively eroded at the rate of 1-10 atomic layers per second. The spatial resolution is better than 1 micrometer for an imaged area 250 micrometer in diameter and a section thickness of 1-2000 nm; thus, the analytical images are element distributions representative of 3-6000 atomic layers. Distributional images can be obtained for many nuclides, whether stable or radioactive, natural or artificially administered.     

Systemic bone-seeking radionuclides for palliation of painful osseous metastases: current concepts

Bone metastases require multidisciplinary treatment, the primary goal of which is to relieve pain and improve quality of life. Among the options available, bone-seeking radioisotopes are attractive because they can treat several symptomatic metastases simultaneously. This therapy may have antitumor efficacy in addition to analgesic properties. Although the ultimate place of systemic radionuclides in the treatment of bone metastases has not been firmly established, some patients clearly benefit from these modalities.