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Background: Demographic change and the medical imperative to accompany patients at all times and also in the case of illness leading to death require good basic knowledge of palliative care in large parts of the medical profession. Palliative care has been introduced into undergraduate medical education as a compulsory subject: “interdisciplinary subject 13 palliative care” (Q13). While course concepts for Q13 have already been positively evaluated, assessment of the consolidation and practical relevance of the knowledge taught is lacking.Methods: Assessment of the consolidation of the learning content from Q13 after the practical year (the “practical year” is the sixth and final year of undergraduate medical education in Germany) by means of a survey with a proven questionnaire and integrated qualitative free-text analysis of a cohort of medical students (n=176) who had already participated in an evaluation before and after Q13.Results: The response rate was 96% after Q13 and 45% after the practical year (PY). Teaching was predominantly perceived as more helpful than the PY (p

During humanitarian crises, such as a pandemic, healthcare systems worldwide face unknown challenges. This study aimed to explore and describe the effect of the SARS-CoV-2 pandemic on the needs of non-infected patients and family caregivers in specialist palliative care, using qualitative, semi-structured interviews. Data were analyzed using inductive content analysis, following the framework approach. Thirty-one interviews were conducted with patients/family caregivers (15/16) in palliative care units/specialist palliative home care (21/10) from June 2020 to January 2021. Well-known needs of patients and family caregivers at the end of life remained during the pandemic. Pandemic- dependent themes were (1) implications of the risk of contagion, (2) impact of the restriction of social interactions, (3) effects on the delivery of healthcare, and (4) changes in the relative's role as family caregiver. Restriction on visits limited family caregivers' ability to be present in palliative care units. In specialist palliative home care, family caregivers were concerned about the balance between preserving social contacts at the end of life and preventing infection. Specialist palliative care during a pandemic needs to meet both the well-known needs at the end of life and additional needs in the pandemic context. In particular, attention should be given to the needs and burden of family caregivers, which became more multifaceted with regards to the pandemic. [ABSTRACT FROM AUTHOR]

Background/Aims: The aim of this study is to investigate the acceptance and benefits of two different strategies to timely integrate specialist palliative care (SPC) in routine cancer care: commonly recommended early SPC counselling versus an informational brochure plus SPC counselling upon patients' request. Methods: Patients diagnosed with incurable cancer within the last 6–12 weeks were sequentially randomized. Endpoints were acceptance of the two strategies after 3 months as well as the use of SPC counselling and psychosocial support, presence of advance directives, palliative care outcome (Integrated Palliative care Outcome Scale [IPOS]), and psychosocial distress (Distress Thermometer [DT]) after 3 and 6 months. In a qualitative part, SPC consultations were analyzed using a content analysis. Results: Overall, 43 patients received SPC counselling and 37 a brochure with SPC counselling on demand. In the brochure group, only one patient later registered for SPC counselling from own initiative. SPC timing was appropriate in 70% of patients (75% counselling/61% brochure, n.s.). Sufficiency, helpfulness and relevance of information, provision of security, and help with finding contacts for specific support were perceived adequate in both groups. No significant differences were found regarding potential effects of the interventions on IPOS or DT after 3 and 6 months. The use of psychosocial support was comparable between the groups and 4 patients had new advance directives (3 counselling/1 brochure). Five key themes of SPC consultations were identified: symptoms, rapport, coping, illness understanding, and advance care planning. Conclusions: Both SPC integration strategies were well accepted. However, patients seem not to benefit from a brochure in terms of initiating SPC counselling timely after a palliative cancer diagnosis. [ABSTRACT FROM AUTHOR]

Background: The Surprise Question ('Would I be surprised if this patient died within 12 months?') identifies patients in the last year of life. It is unclear if 'surprised' means the same for each clinician, and whether their responses are internally consistent. Aim: To determine the consistency with which the Surprise Question is used. Design: A cross-sectional online study of participants located in Belgium, Germany, Italy, The Netherlands, Switzerland and UK. Participants completed 20 hypothetical patient summaries ('vignettes'). Primary outcome measure: continuous estimate of probability of death within 12 months (0% [certain survival]–100% [certain death]). A threshold (probability estimate above which Surprise Question responses were consistently 'no') and an inconsistency range (range of probability estimates where respondents vacillated between responses) were calculated. Univariable and multivariable linear regression explored differences in consistency. Trial registration: NCT03697213. Setting/participants: Registered General Practitioners (GPs). Of the 307 GPs who started the study, 250 completed 15 or more vignettes. Results: Participants had a consistency threshold of 49.8% (SD 22.7) and inconsistency range of 17% (SD 22.4). Italy had a significantly higher threshold than other countries (p = 0.002). There was also a difference in threshold levels depending on age of clinician, for every yearly increase, participants had a higher threshold. There was no difference in inconsistency between countries (p = 0.53). Conclusions: There is variation between clinicians regarding the use of the Surprise Question. Over half of GPs were not internally consistent in their responses to the Surprise Question. Future research with standardised terms and real patients is warranted. [ABSTRACT FROM AUTHOR]

Background: Recognized disparities in quality of end‐of‐life care exist. Our aim was to assess the quality of care for patients dying from cancer, as perceived by bereaved relatives, within hospitals in seven European and South American countries. Materials and Methods: A postbereavement survey was conducted by post, interview, or via tablet in Argentina, Brazil, Uruguay, U.K., Germany, Norway, and Poland. Next of kin to cancer patients were asked to complete the international version of the Care Of the Dying Evaluation (i‐CODE) questionnaire 6–8 weeks postbereavement. Primary outcomes were (a) how frequently the deceased patient was treated with dignity and respect, and (b) how well the family member was supported in the patient's last days of life. Results: Of 1,683 potential participants, 914 i‐CODE questionnaires were completed (response rate, 54%). Approximately 94% reported the doctors treated their family member with dignity and respect "always" or "most of the time"; similar responses were given about nursing staff (94%). Additionally, 89% of participants reported they were adequately supported; this was more likely if the patient died on a specialist palliative care unit (odds ratio, 6.3; 95% confidence interval, 2.3–17.8). Although 87% of participants were told their relative was likely to die, only 63% were informed about what to expect during the dying phase. Conclusion: This is the first study assessing quality of care for dying cancer patients from the bereaved relatives' perspective across several countries on two continents. Our findings suggest many elements of good care were practiced but improvement in communication with relatives of imminently dying patients is needed. (ClinicalTrials.gov Identifier: NCT03566732). Implications for Practice: Previous studies have shown that bereaved relatives' views represent a valid way to assess care for dying patients in the last days of their life. The Care Of the Dying Evaluation questionnaire is a suitable tool for quality improvement work to help determine areas where care is perceived well and areas where care is perceived as lacking. Health care professionals need to sustain high quality communication into the last phase of the cancer trajectory. In particular, discussions about what to expect when someone is dying and the provision of hydration in the last days of life represent key areas for improvement. Disparities exist in the quality of end‐of‐life care. This article assesses the quality of care for dying cancer patients, as perceived by bereaved relatives, within hospitals in seven European and South American countries. [ABSTRACT FROM AUTHOR]

Background: The ERANet-LAC CODE (Care Of the Dying Evaluation) international survey assessed quality of care for dying cancer patients in seven countries, by use of the i-CODE questionnaire completed by bereaved relatives. The aim of this sub study was to explore which factors improve or reduce quality of end-of-life (EOL) care from Norwegian relatives' point of view, as expressed in free text comments. Methods: 194 relatives of cancer patients dying in seven Norwegian hospitals completed the i-CODE questionnaire 6–8 weeks after bereavement; recruitment period 14 months; response rate 58%. Responders were similar to non-responders in terms of demographic details.104 participants (58% spouse/partner) added free text comments, which were analyzed by systematic text condensation. Results: Of the 104 comments, 45% contained negative descriptions, 27% positive and 23% mixed. 78% described previous experiences, whereas 22% alluded to the last 2 days of life. 64% of the comments represented medical/surgical/oncological wards and 36% palliative care units. Four main categories were developed from the free text comments: 1) Participants described how attentive care towards the practical needs of patients and relatives promoted dignity at the end of life, which could easily be lost when this awareness was missing. 2) They experienced that lack of staff, care continuity, professional competence or healthcare service coordination caused uncertainty and poor symptom alleviation. 3) Inadequate information to patient and family members generated unpredictable and distressing final illness trajectories. 4) Availability and professional support from healthcare providers created safety and enhanced coping in a difficult situation. Conclusions: Our findings suggest that hospitals caring for cancer patients at the end of life and their relatives, should systematically identify and attend to practical needs, as well as address important organizational issues. Education of staff members ought to emphasize how professional conduct and communication fundamentally affect patient care and relatives' coping. [ABSTRACT FROM AUTHOR]

A retractable larynx and adaptations of the vocal folds in the males of several polygynous ruminants serve for the production of rutting calls that acoustically announce larger than actual body size to both rival males and potential female mates. Here, such features of the vocal tract and of the sound source are documented in another species. We investigated the vocal anatomy and laryngeal mobility including its acoustical effects during the rutting vocal display of free‐ranging male impala (Aepyceros melampus melampus) in Namibia. Male impala produced bouts of rutting calls (consisting of oral roars and interspersed explosive nasal snorts) in a low‐stretch posture while guarding a rutting territory or harem. For the duration of the roars, male impala retracted the larynx from its high resting position to a low mid‐neck position involving an extensible pharynx and a resilient connection between the hyoid apparatus and the larynx. Maximal larynx retraction was 108 mm based on estimates in video single frames. This was in good concordance with 91‐mm vocal tract elongation calculated on the basis of differences in formant dispersion between roar portions produced with the larynx still ascended and those produced with maximally retracted larynx. Judged by their morphological traits, the larynx‐retracting muscles of male impala are homologous to those of other larynx‐retracting ruminants. In contrast, the large and massive vocal keels are evolutionary novelties arising by fusion and linear arrangement of the arytenoid cartilage and the canonical vocal fold. These bulky and histologically complex vocal keels produced a low fundamental frequency of 50 Hz. Impala is another ruminant species in which the males are capable of larynx retraction. In addition, male impala vocal folds are spectacularly specialized compared with domestic bovids, allowing the production of impressive, low‐frequency roaring vocalizations as a significant part of their rutting behaviour. Our study expands knowledge on the evolutionary variation of vocal fold morphology in mammals, suggesting that the structure of the mammalian sound source is not always human‐like and should be considered in acoustic analysis and modelling. [ABSTRACT FROM AUTHOR]

Background: Early integration of palliative care can improve outcomes for people with cancer and non-cancer diagnoses. However, prediction of survival for individuals is challenging, in particular in patients with haematological malignancies who are known to have limited access to palliative care. The 'Surprise'-Question can be used to facilitate referral to palliative care. Aim: To explore experiences, views and perceptions of haemato-oncologists on the use of the 'Surprise'-Question in the haemato-oncology outpatients clinics of a university hospital in Germany. Design: A qualitative study using individual semi-structured interviews transcribed verbatim and analysed thematically based on the framework approach. Setting/participants: The study took place at the haemato-oncology outpatient clinic and the bone marrow transplantation outpatient clinic of a university hospital. Nine haemato-oncologists participated in qualitative interviews. Results: Thematic analysis identified 4 themes and 11 subthemes: (1) meaning and relevance of the 'Surprise'-Question; (2) feasibility; (3) the concept of 'surprise' and (4) personal aspects of prognostication. A key function of the 'Surprise'-Question was to stimulate intuition and promote patient-centred goals of care by initiating a process of pause → reflection → change of perspective. It was easy and quick to use, but required time and communication skills to act on. Participants' training in palliative care enhanced their willingness to use the 'Surprise'-Question. Conclusion: Irrespective of its use in prognostication, the 'Surprise'-Question is a valuable tool to facilitate consideration of patient-centred goals and promote holistic care in haemato-oncology. However, prognostic uncertainty, lack of time and communication skills are barriers for integration into daily practice. Further research should involve haematology patients to integrate their needs and preferences. [ABSTRACT FROM AUTHOR]

Background: The provision of care for dying cancer patients varies on a global basis. In order to improve care, we need to be able to evaluate the current level of care. One method of assessment is to use the views from the bereaved relatives. Aim: The aim of this study is to translate and pre-test the 'Care Of the Dying Evaluation' (CODETM) questionnaire across seven participating countries prior to conducting an evaluation of current quality of care. Design: The three stages were as follows: (1) translation of CODE in keeping with standardised international principles; (2) pre-testing using patient and public involvement and cognitive interviews with bereaved relatives; and (3) utilising a modified nominal group technique to establish a common, core international version of CODE. Setting/participants: Hospital settings: for each country, at least five patient and public involvement representatives, selected by purposive sampling, fed back on CODETM questionnaire; and at least five bereaved relatives to cancer patients undertook cognitive interviews. Feedback was collated and categorised into themes relating to clarity, recall, sensitivity and response options. Structured consensus meeting held to determine content of international CODE (i-CODE) questionnaire. Results: In total, 48 patient and public involvement representatives and 35 bereaved relatives contributed to the pre-testing stages. No specific question item was recommended for exclusion from CODETM. Revisions to the demographic section were needed to be culturally appropriate. Conclusion: Patient and public involvement and bereaved relatives' perceptions helped enhance the face and content validity of i-CODE. A common, core international questionnaire is now developed with key questions relating to quality of care for the dying. [ABSTRACT FROM AUTHOR]

Background: Patient-reported outcome (PRO) measurement is crucial to assess the benefit of psychotherapeutic interventions. Is repeated assessment of psychometric self-report data possible, as inpatient palliative care patients suffer from physical and psychological symptoms? What is the self-perceived strain caused by the assessment? Objective The main objective of this study was to investigate the feasibility of a repeated comprehensive psychometric self-assessment of inpatient palliative care patients. Secondary objectives were the PROs of the psychometric assessment. Design: We conducted a prospective cohort study. Patients admitted to our palliative care unit (PCU) were reviewed for eligibility within 72 hours. They were asked for weekly self-reports regarding hope (HHI-D), well-being (FACIT-Sp), anxiety and depression (STADI), and quality of life (QoL; EORTC-QLQ-C-30 single item). The strain caused by the assessment was assessed by a numeric rating scale (0-10) and free comments. Results: Within 11 months, 219 patients were admitted to the PCU. In total, 92 patients were eligible. The most frequent exclusion criterion was 'life expectancy <1 week.' A total of 60 patients participated at the first point of measurement. The mean of self-perceived strain (Likert scale 0-10) due to the assessment was 1.44 (SD 1.99) at T1. Twenty-four patients participated twice. Here we found increased scores for physical well-being and QoL. Conclusion: Repeated assessment of psychological conditions is feasible for 27.4% of inpatients at a German PCU. The most limiting factor is life expectancy of only days at admission to the PCU. However, the self-perceived strain is low. [ABSTRACT FROM AUTHOR]

Background: Patients with squamous-cell carcinoma of the head and neck (SCCHN) on palliative therapy usually have a bad prognosis and suffer from various symptoms. With increasing use of targeted agents in cancer patients at the end of life, the correct assignment of therapy-related symptoms becomes increasingly difficult as cancer-related symptoms usually increase as well. Case Report: We report on 2 cases of patients with SCCHN who received multimodal treatment including palliative therapy with cetuximab. Both patients developed severe thoracic and cervicothoracic pain following treatment. In both cases, extensive paraspinal abscess formation proved to be the underlying cause. One patient was treated conservatively; the other one had to undergo surgical intervention. Conclusions: Awareness of multifaceted therapy-related complications is mandatory when patients receive multimodal treatment including targeted therapies. Unexplained pain syndromes in this context should raise suspicions concerning possible infectious complications and should lead to early use of magnetic resonance imaging. [ABSTRACT FROM AUTHOR]

Background: Bereavement support is part of palliative care. Sending out bereavement anniversary cards is one intervention of follow-up support for the bereaved. This study evaluated the suitability of bereavement anniversary cards as an appropriate method in bereavement care. Methods: A questionnaire was sent to each card recipient since the starting point of this practice (October 2014-June 2015). Data was analyzed descriptively. Results: 24 of 68 deliverable questionnaires were returned (response rate 35%). 22 out of 24 recipients felt pleased receiving the card. No participant felt annoyed on receiving the bereavement anniversary card; every participant agreed to at least one positive reaction (i.e. pleased, grateful or consoled). Conclusions: The participants' reactions and opinions about receiving the anniversary card were decidedly positive and indicate the continuation of this practice. Those few less pleased reactions may be related to timing and the first anniversary of the patients' death and therefore an expression of grief rather than a dissatisfaction with bereavement anniversary cards, as such. [ABSTRACT FROM AUTHOR]

Background: Undergraduate palliative care education (UPCE) became mandatory in Germany by 2013. The training in Mainz, addressing fifth-year (5Y) medical students, emphasizes transfer of knowledge and skills. In this study we assessed students' knowledge and students' self-estimation of self-confidence in palliative care (PC) according to Bandura's concept of self-efficacy. Objective: The study objective was to evaluate the effects of the Mainz UPCE on students' self-confidence regarding important domains in PC. Methods: We conducted a prospective questionnaire-based cohort study with a pre-post design. 5Y medical students ( n=329) were asked for self-estimation concerning knowledge, somatic aspects, spiritual and psychological aspects before and after a 7x90-minute teaching course. To assess knowledge, students completed a multiple choice examination at the end of the term. Results: Overall, 156 students completed matched surveys at both points of measurement. The majority of these students felt more confident after the course than before in all aspects of PC ( p<0.0001). All students passed the exam with average scores greater than 90%. Conclusion: A 7x90-minute interactive tutorial in PC for 5Y medical students is feasible and improves both self-efficacy and knowledge of core PC issues. Whether the effects of the course are long-lasting is the objective for further research. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the effect of hyaluronic acid (HA) on proteoglycan (PG) concentration in alginate cultures of human osteoarthritic chondrocytes and to analyze whether HA exhibit anti-degradative effects in the presence of the cytokine IL-1β.Methods: Cartilage samples from ten patients with osteoarthritis of the knee were harvested and chondrocytes were cultivated in alginate beads. Four groups were cultured: control group with and without IL-1β (500 pg/ml) and HA group (100 μg/ml) with and without IL-1β (500 pg/ml). PG concentration was estimated by a dimethylmethylene blue assay. To assess cell proliferation, we measured DNA content fluorometrically.Results: The proliferation rate (DNA) was unchanged in all culture groups. In the control-group PG/DNA (ng/ng) concentration was 27.1±7.2. Supplementation of the medium with HA decreased PG concentration to 25.3±6.9 (p<0.05). After administration of IL-1β PG/DNA concentration dropped to 23.1±6.0 (p<0.01). By contrast HA treatment of IL-1β stimulated chondrocytes did not further decrease PG concentration (23.9±6.1). In fact the negative effect of isolated HA application was inverted if HA was given with IL-1β (p<0.05).Conclusions: In osteoarthritic chondrocytes cultured phenotypically stable, HA could exhibit protective effects only in the presence of the degradative cytokine IL-1β. Thus, the reported anti-inflammatory effects of HA to cartilage matrix seem to be more indirect by blocking degradative effects of cytokines to the matrix. [Copyright &y& Elsevier]

The article discusses a study on palliative care (PC) needs of patients in hemato-oncological wards in Germany. The study involved a group of patients with solid tumors and hematological malignancies. It demonstrated an approach to identify patients with unmet PC needs and the role of nursing staff in recognizing and facilitating consequences in terms of palliative care.

Purpose: We conducted an international survey of bereaved relatives of cancer patients dying in hospitals in seven countries, with the aim to assess and improve the quality of care. The survey used the i-CODE (International Care of the Dying Evaluation) questionnaire. Here, we report findings from the free-text comments submitted with the questionnaires. We explored for topic areas which would potentially be important for improving the quality of care. Further, we examined who reported free-texts and in what way, to reduce bias without ignoring the function the free-texts may have for those contributing., Methods: We used a combined qualitative-quantitative approach: logistic regression analysis to study the effect of respondents' socio-demographic characteristics on the probability of free-texts contributions and thematic analysis to understand the free-text meaning. The primary survey outcomes, (1) how frequently the dying person was treated with dignity and respect and (2) support for the relative, were related to free-text content., Results: In total, 914 questionnaires were submitted; 457/914 (50%) contained free-text comments. We found no socio-demographic differences between the respondents providing free-texts and those who did not. We discovered different types of free-texts ("feedback," "narrative," "self-revelation") containing themes of which "continuity of care," "the one person who can make a difference," and "the importance of being a companion to the dying" represent care dimensions supplementing the questionnaire items. A free-text type of grateful feedback was associated with well perceived support for the relative., Conclusion: Bereaved relatives used the free-texts to report details related to i-CODE items and to dimensions otherwise not represented. They highlighted the importance of the perceived support from human interaction between staff and the dying patient and themselves; and that more than professional competence alone, personal, meaningful interactions have profound importance., (© 2022. The Author(s).)

Poor communication contributes to morbidity and mortality, not only in general medical care but also at the end oflife. This leads to issues relating to symptom control and quality of care. As part of an international project focused on bereaved relatives' perceptions about quality of end-of-life care, we undertook a quality improvement (QI) project in a general hospital in Córdoba city, Argentina.By using two iterative QI cycles, we launched an educational process and introduced a clinical mnemonic tool, I-PASS, during ward handovers. The introduction of the handover tool was intended to improve out-of-hours care.Our clinical outcome measure was ensuring comfort in at least 60% of dying patients, as perceived by family carers, during night shifts in an oncology ward during the project period (March-May 2019). As process-based measures, we selected the proportion of staff completing the I-PASS course (target 60%) and using I-PASS in at least 60% of handovers. Participatory action research was the chosen method.During the study period, 13/16 dying patients were included. We received 23 reports from family carers about the level of patient comfort during the previous night.Sixty-five per cent of healthcare professionals completed the I-PASS training. The percentage of completed handovers increased from 60% in the first Plan-Do-Study-Act (PDSA) cycle to 68% in the second one.The proportion of positive reports about patient comfort increased from 63% (end of the first PDSA cycle) to 87% (last iterative analysis after 3 months). Moreover, positive responses to 'Did doctors and nurses do enough for the patient to be comfortable during the night?' increased from 75% to 100% between the first and the second QI cycle.In conclusion, we achieved the successful introduction and staff training for use of the I-PASS tool. This led to improved perceptions by family carers, about comfort for dying patients., Competing Interests: Competing interests: The ERANet-LAC CODE project: ‘International Care of the Dying Evaluation (CODE): quality of care for cancer patients as perceived by bereaved relatives’ (reference ELAC2015/T07-0545, January 2017–January 2020) was funded through the second Joint Call for Transnational Research and/or Innovation Projects within the ERANet-LAC Framework, cofunded by the European Commission’s seventh Framework Programme (FP7), with the overall aim to improve the quality of care and quality of life of dying patients with cancer., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.)

Purpose The aim of this official guideline coordinated and published by the German Society for Gynecology and Obstetrics (DGGG) and the German Cancer Society (DKG) was to optimize the screening, diagnosis, therapy and follow-up care of breast cancer. Method The process of updating the S3 guideline published in 2012 was based on the adaptation of identified source guidelines. They were combined with reviews of evidence compiled using PICO (Patients/Interventions/Control/Outcome) questions and with the results of a systematic search of literature databases followed by the selection and evaluation of the identified literature. The interdisciplinary working groups took the identified materials as their starting point and used them to develop suggestions for recommendations and statements, which were then modified and graded in a structured consensus process procedure. Recommendations Part 2 of this short version of the guideline presents recommendations for the therapy of primary, recurrent and metastatic breast cancer. Loco-regional therapies are de-escalated in the current guideline. In addition to reducing the safety margins for surgical procedures, the guideline also recommends reducing the radicality of axillary surgery. The choice and extent of systemic therapy depends on the respective tumor biology. New substances are becoming available, particularly to treat metastatic breast cancer.

Purpose The aim of this official guideline coordinated and published by the German Society for Gynecology and Obstetrics (DGGG) and the German Cancer Society (DKG) was to optimize the screening, diagnosis, therapy and follow-up care of breast cancer. Methods The process of updating the S3 guideline dating from 2012 was based on the adaptation of identified source guidelines which were combined with reviews of evidence compiled using PICO (Patients/Interventions/Control/Outcome) questions and the results of a systematic search of literature databases and the selection and evaluation of the identified literature. The interdisciplinary working groups took the identified materials as their starting point to develop recommendations and statements which were modified and graded in a structured consensus procedure. Recommendations Part 1 of this short version of the guideline presents recommendations for the screening, diagnosis and follow-up care of breast cancer. The importance of mammography for screening is confirmed in this updated version of the guideline and forms the basis for all screening. In addition to the conventional methods used to diagnose breast cancer, computed tomography (CT) is recommended for staging in women with a higher risk of recurrence. The follow-up concept includes suggested intervals between physical, ultrasound and mammography examinations, additional high-tech diagnostic procedures, and the determination of tumor markers for the evaluation of metastatic disease.