The KORE-INNOVATION trial, a prospective controlled multi-site clinical study to implement and assess the effects of an innovative peri-operative care pathway for patients with ovarian cancer: rationale, methods and trial design.

BACKGROUND: Advanced ovarian cancer is managed by extensive surgery, which could be associated with high morbidity. A personalized pre-habilitation strategy combined with an 'enhanced recovery after surgery' (ERAS) pathway may decrease post-operative morbidity. PRIMARY OBJECTIVE: To analyze the effects of a combined multi-modal pre-habilitation and ERAS strategy on severe post-operative morbidity for patients with ovarian cancer (primary diagnosis or first recurrence) undergoing cytoreductive surgery. STUDY HYPOTHESIS: A personalized multi-modal pre-habilitation algorithm entailing a physical fitness intervention, nutritional and psycho-oncological support, completed by an ERAS pathway, reduces post-operative morbidity. TRIAL DESIGN: This is a prospective, controlled, non-randomized, open, interventional two-center clinical study. Endpoints will be compared with a three-fold control: (a) historic control group (data from institutional ovarian cancer databases); (b) prospective control group (assessed before implementing the intervention); and (c) matched health insurance controls. INCLUSION CRITERIA: Patients with ovarian, fallopian, or primary peritoneal cancer undergoing primary surgical treatment (primary ovarian cancer or first recurrence) can be included. The intervention group receives an additional multi-level study treatment: (1) standardized frailty assessment followed by (2) a personalized tri-modal pre-habilitation program and (3) peri-operative care according to an ERAS pathway. EXCLUSION CRITERIA: Inoperable disease or neoadjuvant chemotherapy, simultaneous diagnosis of simultaneous primary tumors, in case of interference with the overall prognosis (except for breast cancer); dementia or other conditions that impair compliance or prognosis. PRIMARY ENDPOINT: Reduction of severe post-operative complications (according to Clavien- Dindo Classification (CDC) III-V) within 30 days after surgery. SAMPLE SIZE: Intervention group (n=414, of which approximately 20% insure with the participating health insurance); historic control group (n=198); prospective control group (n=50), health insurance controls (for those intervention patients who are members of the participating health insurance). ESTIMATED DATES FOR COMPLETING ACCRUAL AND PRESENTING RESULTS: The intervention phase started in December 2021 and will continue until June 2023. As of March 2023, 280 patients have been enrolled in the intervention group. The expected completion of the entire study is September 2024. TRIAL REGISTRATION: NCT05256576.

Depression, mood, stress, and Th1/Th2 immune balance in primary breast cancer patients undergoing classical massage therapy.

PURPOSE: Cancer patients frequently suffer from psychological comorbidities such as depression and elevated stress. Previous studies could demonstrate that cancer patients benefit from massage therapy on the physical and psychological level. This pilot study investigates the effects of massage on depression, mood, perceived stress, and the Th1/Th2 ratio in breast cancer patients. METHODS: Thirty-four breast cancer patients were randomly assigned to a massage group (n=17) and a control group (n=17). Patients of the massage group received two 30-min classical massages per week for 5 weeks. At baseline, at the end of the intervention period, and 6 weeks after the end of intervention, patients of both groups completed the Perceived Stress Questionnaire (PSQ), the Patient Health Questionnaire (PHQ), and the Berlin Mood Questionnaire (BFS) and blood was withdrawn for determining cytokine concentrations and the Th1/Th2 ratio. RESULTS: Twenty-nine patients were included in the statistical analysis. Depression (PHQ) and anxious depression (BSF) were significantly reduced immediately after massage compared to the control group. Stress (PSQ) and elevated mood (BSF) did not show significant alterations after massage therapy. Changes of cytokine concentrations and Th1/Th2 ratio were insignificant as well, although there was a slight shift towards Th1 in the massage group over time. CONCLUSIONS: Massage therapy is an efficient treatment for reducing depression in breast cancer patients. Insignificant results concerning immunological parameters, stress, and mood indicate that further research is needed to determine psychological and immunological changes under massage therapy.

The efficacy of classical massage on stress perception and cortisol following primary treatment of breast cancer.

To investigate the efficacy of classical massage on stress perception and mood disturbances, 34 women diagnosed with primary breast cancer were randomized into an intervention or control group. For a period of 5 weeks, the intervention group (n = 17) received biweekly 30-min classical massages. The control group (n = 17) received no additional treatment to their routine health care. The Perceived Stress Questionnaire (PSQ) and the Berlin Mood Questionnaire (BSF) were used and the patients' blood was collected at baseline (T1), at the end of the intervention period (T2), and 6 weeks after T2 (T3). Compared with control group, women in the intervention group reported significantly lower mood disturbances, especially for anger (p = 0.048), anxious depression (p = 0.03) at T2, and tiredness at T3 (p = 0.01). No group differences were found in PSQ scales, cortisol and serotonin concentrations at T2 and T3. However, perceived stress and cortisol serum levels (p = 0.03) were significantly reduced after massage therapy (T2) compared with baseline in the intervention group. Further research is needed to validate our findings.

Severe disease activity and complications of immunosuppressive therapy: a challenge for acute hospital-based rehabilitation in rheumatology.

Acute rehabilitation refers to the multidisciplinary rehabilitative treatment of patients in continuing need of integrated acute and rehabilitative longterm care. As a result of the advances in acute rheumatology and improved emergency services, an increasing number of patients survive episodes of severe disease and complications of immunosuppressive therapy. These patients require not only treatment of their acute medical problems but also specialized multidisciplinary acute rehabilitation starting as early as possible during their hospital stay. We describe 4 typical cases from the major fields of rheumatology. (1) Acute rehabilitation of a 63-year-old woman with rheumatoid arthritis after replacement of both preexisting knee endoprostheses in one session and removal of the left hip endoprosthesis due to infection and sepsis. (2) Rehabilitation of a 29-year-old man with a 7-year history of ankylosing spondylitis who lived in an adjustable easy chair for 2 years due to severe pain prior to admission. (3) A 61-year-old woman with active refractory Wegener's granulomatosis who developed respiratory insufficiency due to aspergillus and pseudomonas pneumonia. (4) The acute rehabilitation of a 21-year-old woman with systemic lupus erythematosus and a history of 14 laparotomies due to severe acute pancreatitis and multiple gut perforations. Acute rehabilitation was complicated by a large defect of the abdominal wall and significant critical illness polyneuropathy. Our report points out differences between acute, postacute, and longterm rehabilitation, describes the mobilization of patients in acute rheumatology units, and defines specific problems encountered in acute hospital-based rehabilitation of rheumatological patients.

Massage therapy reduces physical discomfort and improves mood disturbances in women with breast cancer.

BACKGROUND. A randomized controlled trial was conducted to investigate the efficacy of classical massage treatment in reducing breast cancer-related symptoms and in improving mood disturbances. METHODS. Women diagnosed with primary breast cancer were randomized into an intervention group and a control group. For a period of 5 weeks, the intervention group received bi-weekly 30-min classical massages in the back and head-neck areas. The control group received no additional treatment to their routine healthcare. To evaluate treatment efficacy, the following validated questionnaires were administrated at baseline (T1), at the end of the intervention (T2), and at a followup at 11 weeks (T3): the Short Form-8 Health Survey, the European Organization of Research and Treatment of Cancer quality of life questionnaire breast module (EORTC QLQ-BR23), the Giessen Complaints Inventory (GBB), and the Berlin Mood Questionnaire (BSF). RESULTS. Eighty-six eligible women (mean age: 59 years) were enrolled in the study. A significantly higher reduction of physical discomfort was found in the intervention group compared with the control group at T2 (p=0.001) and at T3 (p=0.038). A decrease in fatigue was also observed. Women in the intervention group reported significantly lower mood disturbances at T2 (p<0.01) but not at T3. The effect of treatment on mood disturbances was significantly higher if a patient was treated continuously by the same masseur. CONCLUSION. Classical massage seems to be an effective adjuvant treatment for reducing physical discomfort and fatigue, and improving mood disturbances in women with early stage breast cancer.

Effect of treatment with low-intensity and extremely low-frequency electrostatic fields (Deep Oscillation) on breast tissue and pain in patients with secondary breast lymphoedema.

OBJECTIVE: To investigate symptoms and functional impairment in women with secondary lymphoedema of the breast following surgical treatment and to assess the therapeutic benefit of treatment with low-intensity and extremely low-frequency electrostatic fields (Deep Oscillation), supplementing manual lymphatic drainage. METHODS: Twenty-one patients were randomized either to the treatment group (n=11): 12 sessions of manual lymphatic drainage supplemented by Deep Oscillation, or to the control group (n=10): manual lymphatic drainage alone. Assessment included subjective pain and swelling evaluation, range of motion of the shoulder and the cervical spine, and analysis of breast volume using a 3D measuring system. RESULTS: Patients had high pain and swelling scores at baseline. Shoulder mobility was impaired in all patients; restriction of cervical spine mobility was common at baseline and declined further in the control group. Deep Oscillation resulted in significant pain reduction in the treatment group. The subjective reported reduction of swelling in both groups was confirmed objectively by 3D measurement only in the treatment group. CONCLUSION: Additional Deep Oscillation supplementary to manual lymphatic drainage can significantly enhance pain alleviation and swelling reduction in patients with secondary breast lymphoedema compared with manual lymphatic drainage alone.

A pilot clinical trial of the effects of coenzyme Q10 on chronic tinnitus aurium.

OBJECTIVE: To determine the short-term effects of coenzyme Q10 (CoQ10) on the antioxidative status and tinnitus expression in patients with chronic tinnitus aurium. STUDY DESIGN: A 16-week prospective nonrandomized clinical trial (n = 20). Tinnitus and Short Form-36 Questionnaires (TQ/SF-36) were evaluated together with the plasma concentrations of CoQ10, malondialdehyde, and the total antioxidant status. RESULTS: The mean plasma CoQ10 concentration rose under external CoQ10 supply and remained elevated after medication stopped without overall effects on the tinnitus score. However, in a subgroup of 7 patients with low initial plasma CoQ10 concentration and significant increase in the plasma CoQ10 level, a clear decrease in the TQ score was observed. CONCLUSION: In patients with a low plasma CoQ10 concentration, CoQ10 supply may decrease the tinnitus expression. SIGNIFICANCE: This is the first study to examine the effect of CoQ10 in chronic tinnitus aurium.