Safety, Efficacy and Distribution of Doxorubicin Loaded Radiopaque Beads in Chemoembolization in Intermediate Stage Hepatocellular Carcinoma (HCC) with Correlation with Local Response.

PURPOSE: The primary objectives of this study were to evaluate safety, and efficacy of Transarterial Chemoembolization (TACE) using doxorubicin-loaded radiopaque microspheres (DC Bead LUMI™) for the treatment of early and intermediate stage Hepatocellular Carcinoma (HCC) not amenable for curative treatments. Distribution of the microspheres was correlated with results post embolization. MATERIALS AND METHODS: This was a prospective, single arm, open label study. The primary outcome measures were distribution of the radiopaque microspheres as showed by computerized tomography (CT) and local response measured by modified Response Evaluation Criteria (mRECIST) after Magnetic Resonance Imaging (MRI). Secondary measures were Time to Progression (TTP) and Overall Survival (OS). RESULTS: Fifty patients were enrolled over 36 months. Median age was 69.0 years; mean sum of target lesions diameters was 78.6 ± 36.8 mm. There were no Grade 4 or 5 adverse events (AEs). At 6 months Complete Response (CR) (18%), Partial Response (PR) (62%), Objective Response OR (80%) and Stable Disease (SD) (20%) were recorded. Before embolization, Diffusion Weighted Imaging (DWI) showed high signal (restricted diffusion). Post procedure, patients with dense deposition (< 5 mm distance of microsphere aggregations) showed 100% absence of enhancement and no restriction in 30.6%. Median TTP was 8.3 months. TTP for patients with CR was 13.3 months and 7.2 and 5.6 for PR and SD, respectively. At 6 and 36 months, survival was 94% and 34%, respectively. CONCLUSION: DC Bead LUMI™ is well tolerated and effective in early and intermediate stage HCC with maximal necrosis obtained in dense deposition in the target.

Locus of control and distressing symptoms in young cancer patients when assessing depression.

PURPOSE: The aim of the current study was to evaluate the correlation between depression, sense of control (internal and external) and cancer-related distressing symptoms in younger patients (<65 years) with locally advanced or metastatic cancer, and to investigate their potential predictive role when screening for depression. METHODS: 70 patients completed the Beck Depression Inventory (BDI), the Cancer Locus of Control Scale, the Linear Analogue System Assessment (LASA) (for Quality of Life/ QoL) and the M.D. Anderson Symptom Inventory (MDASI). Distressing symptoms, QoL, and locus of control (LOC) were correlated with the presence of depression. RESULTS: The total BDI score was suggestive of depression. In univariate analysis significant correlations were found between the presence of depression and poor QoL, low Eastern Cooperative Oncology Group performance status and 'sense of control over the course of cancer' (p<0.0005). Depression was significantly correlated with pain, distress and poor general activity, overall enjoyment of life and relationships (p=0.004), as well as anxiety, fatigue, anorexia, dyspnoea and sleep disturbances (p=0.001). Multivariate analysis demonstrated that poor QoL and 'sense of control over the course of cancer', as well as anxiety, fatigue, anorexia, dyspnoea and sleep disturbances were significantly correlated with depression (p<0.0005). CONCLUSIONS: We suggest that younger cancer patients' poor QoL, 'sense of control over the course of cancer', as well as anxiety, fatigue, anorexia, dyspnoea and sleep disturbances are significantly correlated with the presence of depression and can eventually represent potential screening predictors.

The influence of distressing symptoms to levels of depression in cancer patients.

PURPOSE: Our objectives were to identify the depression and the distressing symptoms in younger and elderly advanced cancer patients. METHODS: : The instruments that have been used were the Beck Depression Inventory (BDI) for younger patients, the Geriatric Depression Scale (GDS) for geriatric patients and the M. D. Anderson Symptom Inventory (MDASI) for the severity and impact of cancer-related symptoms. RESULTS: A trend for significant correlation was found between the GDS and MDASI symptoms for nausea (p=0.058), while a significant correlation was observed for increased sadness (p=0.011), increased constipation (p=0.021), interference of symptoms in mood (p=0.012) and in relations with people (p=0.007); interference of symptoms in mood was the most important risk factor. For younger patients, many statistically significant associations were found between distressing symptoms and depression; however, interference of symptoms in mood (p=0.045) was the only important risk factor. CONCLUSION: Health-care professionals should take into consideration the risk factors for depressive symptoms suggesting a holistic care in advanced cancer patients.

Transient neutropenia in children with febrile illness and associated infectious agents: 2 years' follow-up.

The aim of the study was to identify the relationship of acquired neutropenia with childhood infections and to assess its clinical course, complications, and outcome. Children admitted to two pediatric wards over a 4-year period with febrile neutropenia were prospectively investigated for underlying infections with inflammatory markers, cultures of body fluids, and serological tests. The study included 161 previously healthy children with febrile neutropenia/leukopenia aged (mean ± SD) 3.02 ± 3.86 years (range, 0.1-14). One hundred and thirty-six out of 161 patients (84.5 %) had transient neutropenia (TN), while in 25 patients, neutropenia was chronic (CN) and persisted for ≥180 days. An infectious agent was isolated in 98/161 (60.9 %) cases, in 68.4 % patients with TN, and in 20 % of those with CN (p = 0.001). Among the patients with CN, seven had positive antineutrophil antibodies (autoimmune neutropenia) and four were eventually diagnosed with hematological malignancy. In all age groups, TN was of short duration (<1 month), of mild to moderate severity, and was predominantly associated with viral infections. Two years after diagnosis, 143/161 children (88.8 %) were available for follow-up. One hundred and thirty-seven of 143 (95.8 %) had recovered completely, while the rest remained neutropenic. The latter patients had a benign course despite severe neutropenia. In conclusion, febrile neutropenia during childhood is usually transient, often following viral and common bacterial infections, without serious complications and in the majority of cases it resolves spontaneously. However, in a considerable percentage of patients, neutropenia is discovered incidentally during the course of an infection on the ground of an underlying hematological disease.

Caregivers' anxiety and self-efficacy in palliative care.

This study examined the relationship between caregivers' anxiety supporting a patient with advanced cancer and self-efficacy and their socio-demographic characteristics, and then whether these variables could influence their self-efficacy. One hundred and seven caregivers of advanced cancer patients participated in the study and completed the Greek versions of the State-Trait Anxiety Inventory (STAI) and the General Perceived Self-efficacy Scale (GSE). Significant comparisons were found between State anxiety and female gender (P= 0.009), cohabitation (P= 0.002) and relationship with the patient (P= 0.004); statistically significant associations were found between State, Trait anxiety and self-efficacy scores of caregivers (P < 0.0005 respectively). A multiple regression model (enter method) showed women (P= 0.005), spouses (P= 0.01) and self-efficacy (P= 0.02) as the significant predictors of State anxiety. Furthermore, self-efficacy seemed to be the strongest contributor of trait anxiety (P < 0.0005). Female caregivers and spouses of advanced cancer patients experience more state anxiety levels than men and other caregivers respectively. In addition, caregivers with low self-efficacy are more likely to have elevated anxiety scores than self-efficacious caregivers. These findings can help healthcare professionals focus on some problems common to caregivers of cancer patients and plan appropriate interventions.

Posttraumatic stress disorder and preparatory grief in advanced cancer.

PURPOSE: The purpose of the current study was to investigate the prevalence of posttraumatic stress disorder (PTSD) and its association with sociodemographic variables and preparatory grief in patients with advanced cancer. METHODS: 195 advanced cancer patients participated in the study. Out of them, 170 had PTSD and 25 had other anxiety disorders. The diagnoses were made in strict accordance with Structured Clinical Interview for DSM-IV Axis I disorders (SCID-I)-Clinician version. Patients completed also the Preparatory Grief in Advanced Cancer Patients (PGAC) scale. RESULTS: Patients with PTSD were younger (63.54 ± 12.07 years) than those without PTSD (70.36 ± 13.03 years, p=0.010). Patients with PTSD revealed more preparatory grief (37.69 ± 12.11) than those without PTSD (29.58 ± 14.04, p= 0.003). Multiple logistic regression analysis showed that preparatory grief (p=0.012), and metastatic disease (p=0.009) remained in the model whereas age showed a trend for independent significance (p=0.067). CONCLUSION: In advanced cancer stages, younger patients, those with metastatic disease or patients with elevated scores on preparatory grief seemed to have a greater likelihood to develop PTSD. Thus, given the prevalence of PTSD in advanced cancer patients, health care professionals should be able to better recognize those who are at risk for or exhibit symptoms of this disorder so that appropriate treatment referrals can be made.

PTEN expression in non small cell lung carcinoma based on digitized image analysis.

PURPOSE: HER2 depended signalling pathway is dereg-ulated in a subset of non small cell lung carcinoma (NSCLC). The tumor suppressor gene PTEN (10q21) regulates the HER2/PI3K/Akt signalling pathway. Our aim was to evaluate PTEN protein expression in NSCLC based on a quantitative analysis method correlating also the results with clinicopathological parameters. METHODS: Protein expression was determined by immunohistochemistry (IHC) in 61 paraffin-embedded cases of patients with NSCLC. Digital image analysis (staining intensity levels) was performed in the corresponding immunostained slides. RESULTS: Loss of PTEN expression was observed in 24 (39.34%) cases, low expression in 29 (47.54%) and overexpression in 8 (13.12%) cases. Multivariate analysis determined that PTEN overexpression was associated with lower risk to develop metastases (p=0.05). CONCLUSION: PTEN deregulation is a relatively frequent genetic event in NSCLC, associated with progressive metastatic process in those patients. Because of binding to the ErbB2 receptor, trastuzumab stabilizes and activates PTEN gene, and loss of its expression negatively affects the response rates in such patients.

Differences in levels of self-efficacy and anxiety between cancer and chronically-ill patients attending a Palliative Care Unit.

PURPOSE: To investigate the differences in anxiety and self-efficacy beliefs as well as the sociodemographic and clinical characteristics, between cancer and chronically-ill patients. METHODS: A total of 175 patients from a pain relief and palliative care unit participated in this study. Patient sociode-mographic and clinical characteristics were recorded. Patients completed the Greek version of the Spielberger State-Trait Anxiety Inventory (STAI) and the Greek version of the General Perceived Self-Efficacy Scale (GSE). RESULTS: No statistically significant differences were found between the two patient populations regarding self-efficacy. Statistically significant differences were found between chronically-ill and cancer patients in the scales of "emotionality" (p<0.0005), and "self-deprecation" (p<0.0005). Statistically significant negative correlations were found between all STAI scales and self-efficacy for both cancer and chronically-ill patients (r ranged from -0.231 to -0.503). CONCLUSION: Chronically-ill patients experienced increased anxiety compared to cancer patients. Self-efficacy had a significant negative correlation with anxiety between the two groups of patients.

Ethical and Practical Challenges in Implementing Informed Consent in HIV/AIDS Clinical Trials in Developing or Resource-Limited Countries

Background/rationale: Ethical issues regarding HIV/AIDS human research in the developing world remain under continuous evaluation; a critical area of concern includes informed consent. This paper reviews several of the most important ethical and practical aspects of informed consent in HIV research in developing countries. Enhancement of overall understanding of such key issues might promote higher ethical standards of future research. Objectives: The major objective was to address informed consent in human research in non-Western societies; and specifically in HIV clinical trials of affected adults. Secondary end-points included the consent complexities in HIV research involving vulnerable patient populations in resource-limited nations; such as children; adolescents and women. Methods: A systematic review of the published literature using MEDLINE and EMBASE from 1998 until December 2008 was performed; using the search terms `HIV/AIDS'; `informed consent'; `clinical trials'; `developing world'. Results: Ethical complexities such as participants' diminished autonomy; coercion or monetary inducement; language difficulties; illiteracy or lack of true understanding of the entire study; cultural barriers mainly due to communitarianism and social diversities were identified in the 44 studies reviewed. Informed consent of vulnerable patient populations must be tailored to their sex and developmental age; while counselling is fundamental. Children and adolescents' assent must be ensured. Local language is to be used; while trusted community leaders and local cultural representatives may convey information. Discussion: Despite the heterogeneity of studies; similarities were identified. Providing adequate and comprehensive information and assessing the true understanding of the research represent fundamental prerequisites. Potential solutions to the critical areas of concern include peer counselling and meetings with local community leaders or local cultural representation. Conclusions: International investigators of HIV human research should bear in mind these ethical issues and their potential solutions; when trying to ensure ethical research conduct; based on a truly informed and culturally relevant consent

Treatment of Budd-Chiari syndrome by transjugular intrahepatic portosystemic shunt.

Patients with Budd-Chiari syndrome may require therapy with portal decompressive surgery. Transjugular intrahepatic portosystemic shunt has recently emerged as a new treatment alternative to surgical shunting, but reported literature is scarce and its long-term outcome is to be evaluated. The aim of our study was to present two patients with Budd-Chiari syndrome treated with transjugular intrahepatic portosystemic shunt. Two female patients with acute and subacute Budd-Chiari syndrome respectively, uncontrolled by medical therapy, were referred for transjugular intrahepatic portosystemic shunting. Both patients had refractory ascites, while one had hepatic insufficiency. Hepatic vein thrombosis was without definitive etiology in one patient and due to essential thrombocytosis in the other. Transjugular intrahepatic portosystemic shunt was successfully created in both patients; in one a transcaval approach was performed. Bare stents were used in one, while in the other a polytetrafluoroethylene-covered stent-graft. Technical success was 100% with no complications. Ascites resolved in both patients and liver function improved. The first patient remains asymptomatic with good shunt patency 6 months after intervention. The second patient is symptom-free two years after the shunt creation, despite stent occlusion. She remains asymptomatic due to hepatic vein collateral development. In patients with acute or subacute Budd-Chiari syndrome uncontrolled by medical therapy, transjugular intrahepatic portosystemic shunt is highly effective with no complications and an associated mid-term clinical success.

Cerebral metastases of malignant melanoma: contemporary treatment modalities and survival outcome.

The aim of our study was to analyze prognostic factors, effect of treatment and survival outcome of a contemporary cohort of melanoma patients with cerebral metastases and eventually propose new recommendations regarding therapy. Sixty four patients with melanoma brain metastases were treated in our department within a 15-year period. We performed a retrospective analysis of their survival with respect to the type of treatment instituted. Four groups were formed according to treatment: Group A patients treated with surgery followed by radiotherapy; group B temozolomide as first-line treatment and radiotherapy after cerebral disease progression; group C radiotherapy alone; group D supportive care only. Patients* characteristics influenced the selection of treatment modality: Group A (7.8%) patients with a single brain metastasis (p=0.001) and controlled extra-cranial disease (p<0.0001), while Group D (21.8%) patients with ulcerated primary lesions (p=0.010) and uncontrolled extra-cranial disease (p<0.0001). Only group B (26.6%) and C (43.7%) patients with similar characteristics including more than one brain lesion. Median overall survival was 3 months. In univariate analysis, median survival for groups A, B, C and D was 12, 5, 3 and 2 months, respectively (p<0.0001). The survival difference between the surgery and non-surgery groups was statistically significant (p=0.0011). Patients treated with supportive care had the worse prognosis (p<0.0001). A survival benefit for patients receiving first-line treatment with temozolomide, as compared to those receiving radiotherapy alone was noted (p=0.0267). In multivariate survival analysis, the number of brain lesions (p=0.0138), the absence of uncontrolled extra-cranial disease (p=0.00221) and the type of treatment for the cerebral disease (p=0.0053) remained significant independent survival predictors. Patients' characteristics remain a critical factor for treatment selection. The number of brain metastases, the extent of disease and the type of treatment represent independent survival predictors. Melanoma patients with a single brain metastasis and controlled extra-cranial disease gain a survival benefit, if surgically treated. Including temozolomide in the first-line treatment of melanoma patients with brain metastases who would have been treated with radiotherapy alone, might present a promising future direction affecting the length of survival.

Primary stenting of subclavian and innominate artery occlusive disease: a single center's experience.

PURPOSE: To review immediate and midterm results of primary stenting for innominate and subclavian artery occlusive lesions. METHODS: Retrospective data were collected from 48 consecutive symptomatic patients (27 men and 21 women, median age 64 years) having 49 subclavian and innominate artery lesions treated with stenting. Of the patients 52% had concomitant ischemic heart disease, and 30% had carotid and/or vertebral artery disease. Indication for treatment was vertebrobasilar insufficiency (VBI) in 16.6% of the patients; upper limb ischemia (ULI) in 31.3%; VBI and ULI in 12.5%; transient ischemic attack in 16.7%; angina in 12.5% before or after left internal mammary artery-to-coronary artery bypass grafting; and leg claudication in 10.4% before or after axillofemoral bypass grafting. Balloon-expandable stents were used in 44 lesions and self-expandable stents in 5 lesions. In total, 53 stents were placed in 48 patients. RESULTS: Technical success was 96%, and clinical success 94%. We encountered four complications (two puncture site hematomas, one distal hand embolization and one transient cerebral ischemia). Two patients died within 30 days from other causes, and seven patients were lost to follow-up. Mean follow-up time was 16.7 months (range 0.3 to 68.2). Five patients had recurrent lesions treated by surgical (n = 2) or endovascular (n = 3) means. Cumulative primary patency rate was 91.7% and 77% at 12 and 24 months, respectively. Cumulative secondary patency rate was 96.5% and 91.7% at 12 and 24 months, respectively. CONCLUSION: Stenting of subclavian and innominate artery lesions resulted in immediate resolution of patients' symptoms with durable midterm effect and few complications in a larger patient group with serious comorbid conditions.

Delayed therapy with curative intent in a contemporary prostate cancer watchful-waiting cohort.

OBJECTIVE: To identify predictors of delayed therapy with curative intent, an increasingly common option in contemporary patients with prostate cancer who initially choose watchful waiting. PATIENTS AND METHODS: The characteristics of all patients at one institution and diagnosed with T1-4NXM0 prostate cancer between 1993 and 2000 were prospectively recorded. Factors recorded included: age, tumour stage, histological type, Gleason score, serum prostate specific antigen (PSA) level, prostate volume, PSA density (PSAD), percentage of positive biopsy cores, and the initial treatment selection. Outcomes, including all cancer-directed interventions, all serum PSA values, and initial outcomes of all interventions with curative intent, were determined by review of all medical records and cancer registry data. RESULTS: Of 187 patients on watchful waiting, 175 had stage T1 or T2 cancer and were analysed primarily. Thirty-eight (22%) of these patients received delayed intervention with curative intent (15 radical prostatectomy, 17 external beam radiotherapy, six brachytherapy). Age (P < 0.001) and percentage of positive biopsy cores (P = 0.042) were significant independent predictors of intervention with curative intent. When the PSA doubling time was added to the model it became a significant predictor (P = 0.018), with percentage positive biopsy cores (P = 0.022) and age (P < 0.001). CONCLUSIONS: Therapy with curative intent is common in contemporary patients with prostate cancer who initially choose watchful waiting. Age and percentage positive biopsy cores are independent predictors of such intervention, with PSA doubling time also an independent predictor.

Malignant melanoma metastatic to the gastrointestinal tract.

A retrospective study of 385 melanoma patients was performed, with the goal of evaluating the clinical characteristics, the role of imaging and the impact of treatment on patients with gastrointestinal (GI) metastases. Eighteen patients (4.7%) had GI tract metastases. In 50% the primary lesion was on the lower extremities (P< 0.01), while 61.1% had nodular melanomas (P < 0.01). Imaging and/or endoscopy were undertaken in 72.2% of the patients, yielding positive results in all. Eight patients underwent curative surgery, two received no treatment, while the remaining eight patients had chemotherapy or immunochemotherapy. Long-term palliation was offered to 87.5% of the surgical patients compared with 50% of the patients treated medically. Median survival in the patients treated with surgery was 47.5 months compared with 5.8 months in the medical group (P < 0.01). GI tract metastases were more common in patients with nodular melanoma of the lower extremities. To our knowledge, this is the first study correlating the primary lesion's characteristics with the development of GI tract metastases. Imaging is effective in the diagnosis of GI tract involvement. Melanoma patients with GI tract metastases can benefit from palliation by surgical resection. Survival is improved when such patients are treated with curative surgery.

Malignant fibrous histiocytoma of the trunk metastatic to the liver: treatment with transcatheter intrahepatic chemoembolization.

We report a patient with symptomatic liver metastases as the sole site of recurrence of a previously resected malignant fibrous histiocytoma of the trunk. We treated the patient with two sessions of transcatheter chemoembolization. Tumor regression was achieved, and the patient remained free of symptoms 23 months after the diagnosis of liver involvement, when he died of acute myocardial infarction. To our knowledge, this is the only case of transcatheter chemoembolization of liver metastases from soft-tissue sarcoma reported in the literature. Although it is a single case, it shows that this method may be a promising therapy for this grave disease.