Monika Keller

Breast carcinoma during pregnancy

Breast carcinoma during pregnancy (BCP) is a difficult clinical situation, as it appears to put the health of the mother in conflict with that of the fetus.

Four-Week Prevalence of Mental Disorders in Patients With Cancer Across Major Tumor Entities

PURPOSE To provide the 4-week prevalence estimates of mental disorders in cancer populations. PATIENTS AND METHODS We enrolled adult patients with cancer from in- and outpatient care facilities, using a proportional stratified random sample based on the nationwide cancer incidence in Germany. Patients who scored 9 or above on the Patient Health Questionnaire (PHQ-9) were administered to the standardized computer-assisted Composite International Diagnostic Interview for mental disorders adapted for cancer patients (CIDI-O). A random sample of those with a PHQ-9 score that was less than 9 were selected for a CIDI-O. RESULTS A total of 5,889 patients were identified, which led to 4,020 participants (a 68.3% response rate); of those, 2,141 patients were interviewed. The 4-week total prevalence for any mental disorder was 31.8% (95% CI, 29.8% to 33.8%); this included any anxiety disorder (11.5%; 95% CI, 10.2% to 12.9%), any adjustment disorder (11.1%; 95% CI, 9.7% to 12.4%), any mood disorder (6.5%; 95% CI, 5.5% to 7.5%), any somatoform/conversion disorder (5.3%; 95% CI, 4.3% to 6.2%), nicotine dependence (4.5%; 95% CI, 3.6% to 5.4%), alcohol abuse/dependence (0.3%; 95% CI, 0.1% to 0.6%), any mental disorder resulting from general medical condition (2.3%; 95% CI, 1.7% to 2.9%), and any eating disorder (0%). The highest prevalence for any mental disorder was found in patients with breast cancer (41.6%; 95% CI, 36.8% to 46.4%), followed by patients with head and neck cancer (40.8%; 95% CI, 28.5% to 53.0%). The lowest prevalence was found in patients with pancreatic cancer (20.3%; 95% CI, 8.9% to 31.6%) and stomach/esophagus cancers (21.2%; 95% CI, 12.8% to 29.6%). CONCLUSION Our findings provide evidence for the strong need for psycho-oncological interventions.

Alternative lengthening of telomeres is associated with chromosomal instability in osteosarcomas

Telomere maintenance is regarded as a key mechanism in overcoming cellular senescence in tumor cells and in most cases is achieved by the activation of telomerase. However there is at least one alternative mechanism of telomere lengthening (ALT) which is characterized by heterogeneous and elongated telomeres in the absence of telomerase activity (TA). We evaluated the prevalence of TA, gene expression of telomerase subunits and ALT in relation to telomere morphology and function in matrix producing bone tumors and in osteosarcoma cell lines and present evidence of a direct association of ALT with telomere dysfunction and chromosomal instability. Telomere fluorescence in situ hybridization (T-FISH) in ALT cells revealed elongated and shortened telomeres, partly in unusual configurations and loci, dicentric marker chromosomes and signal-free chromosome ends. Free ends give rise to end-to-end associations and may induce breakage-fusion-bridge cycles resulting in an increased number of complex chromosomal rearrangements, as detected by multiplex-FISH (M-FISH). We propose that ALT cannot be seen as an equivalent to telomerase activity in telomere maintenance. Its association with telomere dysfunction and chromosomal instability may have major implications for tumor progression.

Fatigue, serum cytokine levels, and blood cell counts during radiotherapy of patients with breast cancer.

PURPOSE To assess the level of fatigue during the course of adjuvant radiotherapy (RT) of breast cancer patients and its relation to anxiety, depression, serum cytokines, and blood count levels. METHODS AND MATERIALS Forty-one patients who received adjuvant RT after breast-conserving surgery were prospectively studied. All patients underwent RT without concomitant chemotherapy. Patients rated their fatigue with two standardized self-assessment instruments, the Fatigue Assessment Questionnaire and a visual analog scale on fatigue intensity, before RT, during weeks 1-5 of RT, and 2 months after RT completion. In addition, the anxiety and depression levels were assessed with the Hospital Anxiety and Depression Scale. A differential blood cell count and the serum levels of the cytokines interleukin (IL)-1beta, IL-6, and tumor necrosis factor-alpha were determined in parallel to the fatigue assessments. RESULTS Fatigue intensity as assessed with the visual analog scale increased (p <0.001) until treatment week 4 and remained elevated until week 5. Two months after RT, the values had fallen to the pretreatment levels. Fatigue measured with the Fatigue Assessment Questionnaire did not increase significantly during treatment, but the subscores on physical (p = 0.035) and cognitive (p = 0.015) fatigue were elevated during treatment weeks 4 and 5. Affective fatigue did not change significantly. Anxiety, as rated with the Hospital Anxiety and Depression Scale, declined during RT (p = 0.002), but the Hospital Anxiety and Depression Scale depression score did not change significantly. IL-1beta, IL-6, and tumor necrosis factor-alpha levels did not change during therapy and did not correlate with fatigue. Peripheral blood cell levels declined significantly during therapy and were still low 2 months after treatment. Until treatment week 5, lymphocytes were reduced to almost 50% of their initial values. Hemoglobin levels did not correlate with fatigue. CONCLUSIONS We observed an increase in fatigue during adjuvant RT of patients with breast cancer. Fatigue returned to pretreatment levels 2 months after treatment. No evidence was found that anxiety, depression, serum levels of IL-1beta, IL-6, tumor necrosis factor-alpha, or declining hemoglobin levels were responsible for the treatment-induced fatigue.

Psychological distress in cancer patients assessed with an expert rating scale.

The purpose of this study was to investigate psychosocial stress in a large sample of cancer patients using an expert rating scale. Specific aims were to analyse the relevance of setting variables (type of clinic, contact initiative, therapy) and gender. A total of 6365 patients were assessed in 105 institutions. Univariate and multivariate statistical analysis of setting variables indicated that patients treated in palliative care settings showed highest distress scores compared to patients recruited from hospitals and outpatient clinics (P<0.001). Significant differences were also found for contact initiative (P<0.001); lowest distress was found in patients who were recruited by routine contact. Patients who asked for psychosocial support or who were recruited by the medical staff showed the highest distress scores. The analysis of therapy groups showed that patients receiving radiotherapy or surgery were not more distressed than patients without therapy. The most distressing treatment was chemotherapy. Gender had differential effects on clinic type (P<0.001) and contact initiative (P<0.001) but not on treatment and diagnosis. Expert rating scales are an important complement for self-assessment questionnaires to evaluate psychological distress of cancer patients in psychosocial studies as well as in routine medical care.

Comprehensive Genetic Counseling for Families At Risk for HNPCC: Impact on Distress and Perceptions

The aim of the study was to explore distress and health beliefs before and after comprehensive interdisciplinary counseling in families at risk for hereditary non-polyposis colorectal cancer (HNPCC). Results reported here were derived from a consecutive sample of 65 counselees [31 patients with colorectal cancer (CRC) and 34 unaffected at-risk persons] who participated in interdisciplinary counseling provided by human geneticists, surgeons, and psycho-oncologists before genetic testing. Data were collected from self-administered questionnaires before, as well as 4-6 weeks after, counseling. Distress and perceptions specific to HNPCC were assessed at both timepoints using standardized as well as author-derived instruments. Distress declined after counseling, as did worries related to HNPCC. An increase was found in personal belief in control of cancer risk, for instance, in the perceived efficacy of early detection of CRC. We also observed a trend toward greater anticipated ability to cope with a positive gene test after counseling. Changes after counseling were generally more pronounced for persons at risk, as compared to patients with cancer. The decrease in distress was partly attributable to an increase in personal self-confidence. One-third of the sample reported enhanced communication specific to hereditary disease within the family after counseling. A substantial minority, however, said they experienced increased worry and physical symptoms after counseling. Overall, counselees demonstrated less stress and perceived cancer threat as well as enhanced beliefs regarding personal control over cancer, suggesting an overall beneficial impact of comprehensive counseling. Further research is needed to identify those individuals most at risk for increased fear and worry related to HNPCC so that they may be most appropriately counseled.

Prevalence of mental disorders, psychosocial distress and need for psychosocial support in cancer patients – study protocol of an epidemiological multi-center study

BackgroundEmpirical studies investigating the prevalence of mental disorders and psychological distress in cancer patients have gained increasing importance during recent years, particularly with the objective to develop and implement psychosocial interventions within the cancer care system. Primary purpose of this epidemiological cross-sectional multi-center study is to detect the 4-week-, 12-month-, and lifetime prevalence rates of comorbid mental disorders and to further assess psychological distress and psychosocial support needs in cancer patients across all major tumor entities within the in- and outpatient oncological health care and rehabilitation settings in Germany.Methods/DesignIn this multicenter, epidemiological cross-sectional study, cancer patients across all major tumor entities will be enrolled from acute care hospitals, outpatient cancer care facilities, and rehabilitation centers in five major study centers in Germany: Freiburg, Hamburg, Heidelberg, Leipzig and Würzburg. A proportional stratified random sample based on the nationwide incidence of all cancer diagnoses in Germany is used. Patients are consecutively recruited in all centers. On the basis of a depression screener (PHQ-9) 50% of the participants that score below the cutoff point of 9 and all patients scoring above are assessed using the Composite International Diagnostic Interview for Oncology (CIDI-O). In addition, all patients complete validated questionnaires measuring emotional distress, information and psychosocial support needs as well as quality of life.DiscussionEpidemiological data on the prevalence of mental disorders and distress provide detailed and valid information for the estimation of the demands for the type and extent of psychosocial support interventions. The data will provide information about specific demographic, functional, cancer- and treatment-related risk factors for mental comorbidity and psychosocial distress, specific supportive care needs and use of psychosocial support offers.

Development and psychometric evaluation of the Basic Documentation for Psycho-Oncology, a tool for standardized assessment of cancer patients

OBJECTIVE This study describes the development and psychometric evaluation of the Basic Documentation for Psycho-Oncology (PO-Bado), an expert rating scale designed for the comprehensive assessment of psychosocial and physical distress in cancer patients. While there are many self-report measures (usually used for screening purposes), the PO-Bado is the first standardized clinician-administered instrument to guide professionals in a focused and structured psycho-oncological assessment. METHODS The validation procedure was performed in 596 patients from different settings of cancer care, including all cancer sites and stages of the disease. The psychometric evaluation included (a) determination of the factorial structure, (b) homogeneity of scales and interrater reliability, (c) convergent and discriminant validities, and (d) examination of sensitivity to change. RESULTS The final version of the PO-Bado includes two scales: the physical distress scale (four items) and the psychological distress scale (eight items). A manual and an interview guideline were developed alongside. The psychometric properties suggest that the PO-Bado is a reliable and valid tool used to assess and to differentiate the distress of patients with cancer, as well as treatment-related changes in distress. CONCLUSION We suggest that the PO-Bado is a useful tool that is applicable in different oncology settings. It complements self-report measures and provides a structured format for focused psycho-oncological assessment and intervention. The two-dimensional structure allows differentiation between physical and psychological problems, assisting professionals in their diagnostic efforts and in providing appropriate support or treatment. When used consistently across professions and settings, the PO-Bado can form the basis for audit and interdisciplinary communication.

The Basic Documentation for Psycho-Oncology (PO-Bado) – an Expert Rating Scale for the Psychosocial Experience of Cancer Patients

Background: The integration of psycho-oncology into the medical care of cancer patients requires a transparent, reliable, and valid assessment of psychosocial stress. The Basic Documentation for Psycho-Oncology (PO-Bado), including a short version and a breast cancerspecific version, is such an instrument. The purpose of this article is to present the current stage of development of the 3 versions. Patients and Methods: All versions of the PO-Bado were developed and psychometrically evaluated based on the empirical analysis of multiple oncological samples. External criteria for the validation and determination of cut-off scores were the Hospital Anxiety and Depression Scale, the Questionnaire on Stress in Cancer Patients, and the EORTC Quality of Life Questionnaire. Inter-rater reliability was examined by different psycho-oncologists who independently rated PO-Bado interviews. Results: Three versions of the PO-Bado are presented: the standard version (PO-Bado, 17 items), the short form (PO-Bado SF, 7 items), and the breast cancerspecific version (PO-Bado BC, 21 items). A manual and interview guideline are provided for all versions. By now, the standard version has been implemented throughout Germany and includes data of 6,365 patients. Conclusion: A consistent nationwide implementation of the PO-Bado for the assessment of psychosocial stress in cancer patients would contribute to the improvement of medical care.

Effect of Parathyroidectomy on Quality of Life and Neuropsychological Symptoms in Primary Hyperparathyroidism

Neuropsychological symptoms are found in a certain number of patients with primary hyperparathyroidism (PHPT). Preoperative and postoperative quality of life, anxiety, and depression are measured to analyze the impact of parathyroidectomy on these symptoms. In this prospective study, 66 patients underwent parathyroidectomy for PHPT and were evaluated pre- and postoperatively with two validated psychometric instruments (HADS, PHQ-9). Health-related quality of life was measured with a 12-item short-form health survey (SF-12). Preoperatively, the median physical component score (SF-12) of 43.0 and mental component score of 43.5 were lower than those of the general population (52.8 and 54.2 points, respectively). One year postoperatively the mental component score increased to 48.6 (p = 0.011), whereas the physical functioning scale scored 45.3 and therefore did not change significantly (p = 0.585). Preoperatively, symptoms of depression were found in 23.4% of the patients, and 15.6% of the patients displayed symptoms of anxiety (HADS). The prevalence of depression was significantly higher in patients with preoperative serum calcium levels > 11.2 mg/dl (2.8 mmol/L) (p = 0.015). Twelve months postoperatively, the overall proportion of patients with anxiety and depression decreased to 7.8% and 15.7%, respectively (p = NS). The severity of depression as measured with the PHQ-9 declined postoperatively as well. In this study, preoperative neuropsychological symptoms were related to the serum calcium levels. Postoperative health-related quality of life improved significantly. Among patients with preoperative symptoms of depression and anxiety, both symptoms were alleviated significantly at the 12-month follow-up. Therefore, surgery for PHPT seems to be effective in reducing neuropsychological morbidity associated with PHPT.