Predictive implications of bone turnover markers after palliative treatment with (186)Re-HEDP in hormone-refractory prostate cancer patients with painful osseous metastases.

PURPOSE: To prospectively evaluate the predictive value of various bone formation and resorption markers in patients with bone metastases from prostate cancer after palliative treatment with (186)Re-1,1-hydroxyethylidene diphosphonate ((186)Re-HEDP). METHODS: Included in the study were 36 men with prostate cancer, suffering from painful osseous metastases and treated with (186)Re-HEDP. None had received any treatment that would have interfered with bone metabolism before (186)Re-HEDP treatment or throughout the follow-up period. For each patient, pretreatment and posttreatment serum levels of osteocalcin (OC), bone alkaline phosphatase (BALP), aminoterminal (PINP) and carboxyterminal (PICP) propeptides of type I collagen, amino-terminal (NTx) and carboxyterminal (CTx) telopeptides of type I collagen and their combinations were compared with the level and duration of pain response to radionuclide treatment. RESULTS: Pain response was correlated only with pretreatment NuTaux/PINP, PICP/PINP and NTx/CTx ratios and posttreatment decrease in baseline NTx and PICP values (p = 0.0025-0.035). According to multivariate and ROC analyses, the best marker-derived predictors of better and longer duration of response to (186)Re-HEDP treatment were a posttreatment decrease in NTx of > or = 20% (RR = 3.44, p = 0.0005) and a pretreatment NTx/PINP ratio of > or = 1.2 (RR = 3.04, p = 0.036) CONCLUSION: NTx, a potent collagenous marker of bone resorption, along with the novel NTx/PINP ratio provide useful cut-off values for identifying a group of patients suffering from painful osseous metastases from hormone-refractory prostatic carcinoma who do not respond to palliative treatment with (186)Re-HEDP. This information could help avoid an inefficient and expensive radionuclide treatment. Also, in the cohort of patients who will eventually undergo such treatment, the medium-term posttreatment changes in NTx offer valuable predictive information regarding long-term palliative response.

Illness-related hopelessness in advanced cancer: influence of anxiety, depression, and preparatory grief.

The growing interest in the psychological distress in patients with cancer has been the major reason for the conduction of this study. The aims were to assess the relationship of hopelessness, anxiety, distress, and preparatory grief, as well as their predictive power to hopelessness. Ninety-four patients with advanced cancer completed the study at a palliative care unit in Athens, Greece. Beck Hopelessness Scale, the Greek version of the Hospital Anxiety and Depression (HAD) scale, and the Preparatory Grief in Advanced Cancer Patients scale were administered. Information concerning patients' treatment was acquired from the medical records, whereas physicians recorded their clinical condition. Hopelessness correlated significantly with preparatory grief (r = .630, P < .0005), anxiety (r = .539, P < .0005), depression (r = .642, P < .0005), HAD-Total (r = .686, P < .0005), and age (r = -.212, P = .040). Multiple regression analyses showed that preparatory grief (P < .0005), depression (P < .0005), and age (P = .003) were predictors of hopelessness, explaining 58.8% of total variance. In this patient sample, depression, preparatory grief, and patients' age were predictors of hopelessness.

Does quality of sleep mediate the effect of depression on hopelessness?

The objectives of the study were to evaluate the relationship between sleep quality, depression, and hopelessness in advanced cancer patients and whether sleep quality mediated the effect of depression on hopelessness. The final sample consisted of 102 advanced cancer patients under palliative treatment. Patients completed the Greek Pittsburgh Sleep Quality Index, a sleep quality instrument, the Greek Beck Depression Inventory for measuring depression, and finally the Beck Hopelessness Scale. Patients' performance status was assessed by their overall physical functioning, as defined by the Eastern Cooperative Oncology Group. Depression was highly associated with hopelessness (r = .52, p<.001). Statistically significant associations were found between sleep quality with hopelessness (r = .37, p<.001), as well as with depression (r = .36, p<.001). Mediation analyses indicated that depression influenced hopelessness directly as well as indirectly by its effect on sleep quality. About 14.58% of the variation in hopelessness was explained by depression; 4% of the variance in hopelessness explained by depression was accounted for by the mediation pathway indicating that sleep quality mediated the relationship between depression and hopelessness. Similarly, in the reverse mediation analysis, depression mediated the relationship between sleep quality and hopelessness; 43% of the variation in hopelessness was explained by sleep quality. In conclusion, some of the effect of depression on hopelessness was mediated by sleep quality, but depression had a direct effect on hopelessness as well. Additionally, some of the effect of sleep quality on hopelessness was mediated by depression. The current findings are important because improving sleep quality by treating depression may contribute to decreased hopelessness scores and vice versa: Treating depression by improving sleep quality may also contribute to lower hopelessness scores.

The relationship between quality of life and levels of hopelessness and depression in palliative care.

There is growing interest in the psychological distress and quality of life of cancer patients. The aim of this study was to compare the responses of 102 advanced cancer patients on a quality of life scale (as measured by the SF12) with the Beck Depression Inventory (BDI) and the Beck Hopelessness Scale (BHS), as well as the impact of depression and hopelessness on quality of life. Significant associations were found between gender (P=.027), performance status (P=.003), opioids (P=.002), depression (P<.0005), and hopelessness (P<.0005) with the SF12-Mental Component Score (MCS). Gender (P=.07), metastasis (P=.001), opioids (P=.0005), and education (P=.045) correlated significantly with SF12-Physical Component Score (PCS). In the prediction of MCS, the dimensions of age, hopelessness, gender, and performance status were statistically significantly high (P<.0005), explaining 48% of variance. For PCS, the predictor variables were education, metastasis, and opioids (25% of variance). Quality of life, in this patient population, was predicted by the level of hopelessness and patients' demographic and clinical characteristics.

Bilateral metastases to extraocular muscles from lobular breast carcinoma.

BACKGROUND: Metastastic carcinoma to extraocular muscles is extremely rare, but even more so is the case of a bilateral one. CASE REPORT: A 50-year-old woman with a history of mastectomy for a T4N1M0 right breast carcinoma was referred to us with diplopia due to bilateral extraocular muscle metastases, 5 years post mastectomy. Multiple metastases to the whole body were also present. A combination of high-dose irradiation, hormonotherapy and chemotherapy were performed. RESULTS: Despite the multidisciplinary treatment approach, the diplopia persisted. A literature review revealed only 4 cases of bilateral metastases to extraocular muscles. The present case is the second attributed to lobular carcinoma and the only one treated with a high dose of radiotherapy combined with systemic therapy. CONCLUSION: In a cancer patient, any orbital change must be examined for the possibility of an extraocular metastasis. Conclusions affecting the optimal treatment policy of extraocular muscle metastases are difficult to determine, due to the small number of reported cases.

Post-traumatic growth in advanced cancer patients receiving palliative care.

GOALS OF WORK: To develop the Greek version of the Post-traumatic Growth Inventory (PTGI-Gr), and assess its psychometric properties in a palliative care patient sample. PATIENTS AND METHODS: The scale was translated with the forward-backward procedure to Greek. It was administered twice, with a 3-day interval, to 131 eligible patients with advanced cancer. Together with the PTGI, the patients also completed the Greek version of the Impact of Events Scale-Revised scale (IES-R-Gr). The reliability was assessed by the internal consistency (Cronbach's alpha coefficients), test/retest (Spearman's r value), and inter-item correlations. Validity was demonstrated by factor analysis, inter-scale correlations, construct validity with the IES-R-Gr, and combined with the Eastern Cooperative Oncology Group (ECOG) performance status. MAIN RESULTS: The PTGI-Gr yielded a five-factor structure, explaining 73.5% of the variance. Cronbach's alphas for the five factors ranged from .66 to .87, respectively. Overall test-retest reliability was satisfactory with a range between .85 and .92 (p<.0005), and inter-item correlations ranged between .47 and .63. Inter-scale correlations were found satisfactory (p<.0005, p<.005, and p<.05). Validity as performed using combined validity analysis showed good results. Satisfactory construct validity was supported by the correlation analysis between the PTGI-Gr and the IES-R-Gr scales. CONCLUSIONS: PTGI-Gr is an instrument with satisfactory psychometric properties, and is a valid research tool for the post-traumatic growth of advanced cancer patients.

Demographic and clinical predictors of spirituality in advanced cancer patients: a randomized control study.

AIM: To study the influence of cancer patients' sociodemographic and clinical characteristics in their spiritual beliefs and attitudes. BACKGROUND: Patients' sociodemographic and clinical characteristics may have an important role in their spirituality. Failure to control these factors can lead to a false estimation on patients' spiritual beliefs. Previous studies have found that age, gender and health status associate with spiritual attitudes and beliefs.Design. Survey. METHODS: The Spiritual Involvement and Beliefs Scale was administered to 82 cancer patients. Demographic characteristics, disease status and treatment regimen were recorded. RESULTS: Among the most significant correlations were those between gender and all the subscales, cancer diagnosis, existential/meditative subscale, radiotherapy treatment and external/ritual, internal/fluid and existential meditative. In the prediction of spirituality, the contribution of gender, age, years of education, performance status and radiotherapy is high. CONCLUSION: Acknowledging the specific patients' demographic and medical characteristics, such as female gender, old age, years of education, performance status and radiotherapy treatment, contributes to the prediction of patients' spiritual beliefs and attitudes. RELEVANCE TO CLINICAL PRACTICE: Addressing spiritual needs in palliative care among the dying needs to be a priority and could be a crucial aspect of psychological functioning, especially when considering certain demographic and clinical characteristics.

Euthanasia and physician-assisted suicide in cases of terminal cancer: the opinions of physicians and nurses in Greece.

The aim of this study was to investigate the opinions of physicians and nurses on euthanasia and physician-assisted suicide in advanced cancer patients in Greece. Two hundred and fifteen physicians and 250 nurses from various hospitals in Greece completed a questionnaire concerning issues on euthanasia and physician-assisted suicide. More physicians (43.3%) than nurses (3.2%, p < 0.0005) reported that in the case of a cardiac or respiratory arrest, they would not attempt to revive a terminally ill cancer patient. Only 1.9% of physicians and 3.6% of nurses agreed on physician-assisted suicide. Forty-seven per cent of physicians and 45.2% of nurses would prefer the legalization of a terminally ill patient's hastened death; in the case of such a request, 64.2% of physicians and 55.2% of nurses (p = 0.06) would consider it if it was legal. The majority of the participants tended to disagree with euthanasia or physician-assisted suicide in terminally ill cancer patients, probably due to the fact that these acts in Greece are illegal.

The experience of hopelessness in a population of Greek cancer patients receiving palliative care.

BACKGROUND: Beck Hopelessness Scale (BHS) has been translated and validated in many languages. AIM: The validation of the English version of BHS in advanced cancer patients receiving palliative treatment in Greece. METHODS: The final sample was 112 advanced cancer patients. Internal consistency, item-total correlations, and test-retest using four different approaches were calculated for the assessment of the reliability. Construct validity was used by examining correlations between BHS, Hospital Anxiety and Depression Scale (HAD-Depression) and the Schedule of Attitudes toward Hastened Death (SAHD). Known-groups validity was also assessed by detecting group differences according to disease severity as measured by the Eastern Cooperative Oncology Group (ECOG) performance status. Univariate and multivariate analyses were constructed to explore the relationship between hopelessness, depression, hastened death and the patients' demographic and clinical characteristics. RESULTS: One factor solution was yielded accounted for 46.64% of the variance. The test-retest reliability was satisfactory (p < 0.0005). Validity as performed using known-group analysis showed good results. Most significant correlations were found between BHS, ECOG (p = 0.018) and gender (p = 0.08). The strongest predictors were gender (p = 0.050) and ECOG (p = 0.045). CONCLUSIONS: BHS seemed to be a useful instrument to assess pessimistic attitude and hopelessness in a Greek cancer population, with valid psychometric properties.

Psychometric properties of the Impact of Event Scale in Greek cancer patients.

To develop the Greek version of the Impact of Event Scale-Revised (IES-R-Gr), assess its psychometric properties, and finally to examine the impact of cancer diagnosis to a palliative care patient sample, the IES-R was translated into Greek using the "forward-backward" procedure. It was administered twice, at one-week intervals, to 82 eligible patients with advanced cancer. Together with the IES-R-Gr scale, the patients also completed the Hospital Anxiety and Depression (HAD) Scale. Reliability was assessed in terms of internal consistency (Cronbach's alpha coefficients) and test/retest (Spearman's r value and Kendall's tau-b). Construct validity was demonstrated through association with the HAD Scale, and convergence and discriminative validity and interscale correlations were also assessed. The Greek version of the IES-R had Cronbach's alphas for the intrusion, avoidance, and hyperarousal scales of 0.72, 0.77, and 0.85, respectively. Overall test-retest reliability was satisfactory at P<0.0005. Satisfactory construct validity was supported by the correlation analysis between the IES-R-Gr subscales and anxiety and depression. Factor analysis yielded three factors, explaining 57.26% of the variance. Interscale and interitem correlations were found satisfactory at P<0.0005. These results demonstrate that the IES-R-Gr is an instrument with satisfactory psychometric properties and is a valid research tool for the impact of cancer diagnosis in advanced cancer patients.

Sleep quality in advanced cancer patients.

OBJECTIVE: The objective of this study was to evaluate the sleep quality of advanced cancer patients and its relationship with pain, depression, and hopelessness. METHODS: The participants were 102 advanced cancer patients who were on palliative treatment. Patients completed a sleep quality instrument, the Pittsburgh Sleep Quality Index (PSQI); a pain assessment tool, the Greek Brief Pain Inventory; a self-report measure of depression, the Beck Depression Inventory; and, finally, the Beck Hopelessness Scale. RESULTS: Multiple regression analyses (forward method) have shown that hopelessness (P=.003), "interference of pain with mood" (P<.0005), and strong opioids (P=.010) seemed to influence patients' sleep quality (PSOI). In an additional regression analysis (enter method), the PSQI is significantly related to opioids (P=.013), hopelessness (P=.035), and "interference of pain with mood" (P=.004). CONCLUSION: Hopelessness, pain treatment, and "interference of pain with mood" may influence the quality of sleep in advanced stages of cancer.

Comparison of pain quality descriptors in cancer patients with nociceptive and neuropathic pain.

BACKGROUND: The aim of this study was to explore the differences in the descriptors for neuropathic and nociceptive pain in cancer patients. PATIENTS AND METHODS: One hundred and eighty-six cancer patients who participated in the study completed the Greek version of the McGill Pain Questionnaire (G-MPQ) for the assessment of their pain quality. RESULTS: Significant differences were found between type of pain in all G-MPQ classes. Statistically significant associations were found between Present Pain Intensity and type of pain (p = 0.002). Multivariate logistic regression analyses showed that patients who selected the descriptors "pricking" and "annoying" were 2.64 times and 2.2 times, respectively, more likely to experience nociceptive rather than neuropathic pain (p = 0.020 and p = 0.015, respectively). Further analysis showed that sensory seemed to be the most significant indicator for type of pain (95%, CI: 0.911-0.974, p < 0.001). CONCLUSION: Sensory quality and some of pain descriptors may differentiate neuropathic from nociceptive pain in cancer patients.

Traumatic distress and positive changes in advanced cancer patients.

This study investigated the traumatic distress and posttraumatic growth in 58 advanced cancer patients receiving palliative treatment in a Pain Relief and Palliative Care Unit. The patients completed the Greek version of the Impact of Events Scale-Revised and the Posttraumatic Growth Inventory. Statistically significant associations were found among Impact of Events Scale-Revised-Greek "Relating to Others" (r = 0.311, P = .017), "New Possibilities" ( r = 0.248, P = .050), and "Appreciation of Life" ( r = 0.419, P = .001), and the Posttraumatic Growth Inventory scores (r = 0.323, P = .013). Similarly, "Appreciation of Life" correlated significantly with "Avoidance" (r = 0.318, P = .015), "Intrusion" (r = 0.365, P = .005), and "Hyperarousal" (r = 0.398, P = .002). Statistically significant associations were also found between "Relating to Others" and "Intrusion" (r = 0.414, P = .001). The study concluded that in advanced cancer patients, the higher the impact event, the more improvement in their relationships with others, enhanced life appreciation, and more positive consequences after trauma.

Patient-specific dosimetry calculations using mathematic models of different anatomic sizes during therapy with 111In-DTPA-D-Phe1-octreotide infusions after catheterization of the hepatic artery.

UNLABELLED: The aim of the study was to provide dosimetric data on intrahepatic (111)In-diethylenetriaminepentaacetic acid (DTPA)-D-Phe(1)-octreotide therapy for neuroendocrine tumors with overexpression of somatostatin receptors. METHODS: A dosimetric protocol was designed to estimate the absorbed dose to the tumor and healthy tissue in a course of 48 treatments for 12 patients, who received a mean activity of 5.4 +/- 1.7 GBq per session. The patient-specific dosimetry calculations, based on quantitative biplanar whole-body scintigrams, were performed using a Monte Carlo simulation program for 3 male and 3 female mathematic models of different anatomic sizes. Thirty minutes and 2, 6, 24, and 48 h after the radionuclide infusion, blood-sample data were collected for estimation of the red marrow radiation burden. RESULTS: The mean absorbed doses per administered activity (mGy/MBq) by the critical organs liver, spleen, kidneys, bladder wall, and bone marrow were 0.14 +/- 0.04, 1.4 +/- 0.6, 0.41 +/- 0.08, 0.094 +/- 0.013, and (3.5 +/- 0.8) x 10(-3), respectively; the tumor absorbed dose ranged from 2.2 to 19.6 mGy/MBq, strongly depending on the lesion size and tissue type. CONCLUSION: The results of the present study quantitatively confirm the therapeutic efficacy of transhepatic administration; the tumor-to-healthy-tissue uptake ratio was enhanced, compared with the results after antecubital infusions. Planning of treatment was also optimized by use of the patient-specific dosimetric protocol.

Octreotide long-acting formulation (LAR) in chronic loperamide-refractory diarrhea not related to cancer treatment.

OBJECTIVE: The effectiveness and improvement in quality of life (QOL) of a long-acting formulation of octreotide (LAR) administration for cancer patients, with chronic loperamide-refractory diarrhea not attributed to medical therapy, were investigated. PATIENTS AND METHODS: Twenty-nine patients with chronic loperamide-refractory diarrhea were enrolled to receive octreotide LAR at a starting dose of 30 mg i.m. every 28 days until resolution of the diarrhea for a period of 3 months. RESULTS: Twenty-three patients (79.3%) administered octreotide LAR achieved resolution of diarrhea, while six patients (20.7%) successfully controlled their diarrhea during the study. All patients experienced improved sodium, potassium, albumin and total protein values with improvement in their QOL, as assessed by the Linear Analog Scale Assessment (LASA) (mean values at baseline and at 3 months: energy: 3.2+/-1.1 vs. 6.2+/-1.4; function: 3.1+/-1.3 vs. 6.2+/-1.2; QOL: 3.2+/-0.9 vs. 6.1+/-1.4). No toxicities associated with the administration of octreotide LAR were noted. CONCLUSION: The administration of octreotide LAR at a starting dose of 30 mg i.m. every 28 days efficiently resolved or controlled chronic loperamide-refractory diarrhea, not caused by medical intervention, in cancer patients and improved their QOL.

Expression of DNA mismatch repair gene MSH2 in cytological material from lung cancer patients.

Mismatch repair genes encode for proteins responsible for the correction of bases incorrectly paired in the DNA. Loss of DNA mismatch repair activity has been associated with various cancers including tumors of the lung. In the present study, we have analyzed by immunocytochemistry the expression of MSH2 DNA repair gene in cytological material obtained by fine needle aspiration from a panel of 42 primary lung cancer patients. Specimens included 13 adenocarcinomas, 11 small cell carcinomas and 18 squamous cell carcinomas. Loss of expression or low expression was detected in 6 out of 13 (46%) adenocarcinomas and in 7 out of 18 (39%) of squamous cell carcinomas, although all 11 small cell carcinomas expressed MSH2. Our results suggest that loss of MSH2 expression is frequent in nonsmall cell carcinomas of the lung (P < 0.01, chi2 test). Evaluation of MSH2 expression can be applied for the screening of cytological material from fine needle aspirations from the lung.

Oral transmucosal fentanyl citrate: overview of pharmacological and clinical characteristics.

Oral transmucosal fentanyl citrate (OTFC; brand name Actiq, Cephalon, UT) is a new opioid formulation that incorporates fentanyl into a lozenge and allows drug delivery through the buccal mucosa. This kind of absorption avoids first-pass metabolism, yielding a bioavailability substantially greater than oral administration. OTFC has a rapid onset of action and a short duration of effect. These characteristics, which resemble the course of a typical breakthrough pain episode, resulted in making OTFC the first opioid analgesic formulation specifically developed and approved for control of breakthrough pain in cancer patients. Apart from that, OTFC has been used in a variety of clinical situations of noncancer pain. This review article presents the synthesis; clinical pharmacology; pharmacokinetic and pharmacodynamic properties, toxicity, and clinical efficacy of this novel agent.

Assessing spirituality and religiousness in advanced cancer patients.

The aim of this study was to translate the Spiritual Involvement and Beliefs Scale into the Greek language and validate its psychometric properties in a sample of advanced cancer patients treated in a palliative care unit. The scale was translated into Greek with the "forward-backward" procedure. It was administered twice, with a 3-day interval, to 82 patients with advanced cancer. Patients completed the Spiritual Involvement and Beliefs Scale and the Greek Hospital Anxiety and Depression Scale. The scale had an overall Cronbach alpha of 0.89. Overall test-retest reliability was satisfactory at P<.0005. Satisfactory construct validity was supported between the Spiritual Involvement and Beliefs Scale subscales and Hospital Anxiety and Depression subscales. Interscale and interitem correlations were found satisfactory at P<.0005. These results support that the Spiritual Involvement and Beliefs Scale is an instrument with satisfactory psychometric properties and is a valid research tool for spirituality in advanced cancer patients.

The attitudes of Greek physicians and lay people on euthanasia and physician-assisted suicide in terminally ill cancer patients.

The purpose of this article is to explore the attitudes of lay people and physicians regarding euthanasia and physician-assisted suicide in terminally ill cancer patients in Greece. The sample consisted of 141 physicians and 173 lay people. A survey questionnaire was used concerning issues such as euthanasia, physician-assisted suicide, and so forth. Many physicians (42.6%) and lay people (25.4%, P = .002) reported that in the case of a cardiac and/or respiratory arrest, there would not be an effort to revive a terminally ill cancer patient. Only 8.1% of lay people and 2.1% of physicians agreed on physician-assisted suicide (P = .023). Many of the respondents, especially physicians, supported sedation but not euthanasia or physician-assisted suicide. However, many of the respondents would prefer the legalization of a terminally ill patient's hastened death.

A prospective randomized controlled clinical trial of zoledronic acid for bone metastases.

In this study, we assessed the safety, tolerability, and effectiveness of two therapeutic regimens relating to the frequency of zoledronic acid (ZOL) infusion. Sixty adult patients with bone metastases were randomly assigned to two study groups. The first group (group A) received 4 mg ZOL every two weeks, and the second group (group B) received 4 mg ZOL every four weeks. Assessment measures included C-telopeptide (CTX) rate, the Greek Brief Pain Inventory (GBPI), the linear analogue scale assessment (LASA) of quality of life, and biochemical markers. Assessments were made at weeks 12, 24, 36, and 48. Clinical endpoints included effective decrease in bone resorption markers, pain relief and improvement of mobility status. The follow-up period was 48 weeks. No statistically significant differences between groups A and B were found in overall profile of biochemical markers, Eastern Cooperative Oncology Group (ECOG) performance status, and GBPI score at the end of the follow-up period. Assessment of bone metastases revealed a slight difference between the two groups, however this difference was not statistically significant. These findings indicate that administering zoledronic acid at four rather that two weeks has no significant impact on overall outcome.