The impact of whole-body hyperthermia interventions on mood and depression - are we ready for recommendations for clinical application?

Objective: To systematically summarize the findings from research studies examining the effects of whole-body hyperthermia (WBH) interventions on mood and symptoms of depression. Methods: Systematic literature search of online and offline databases (e.g., Pubmed, Web of Knowledge, Cochrane, academic libraries). Risk of bias assessment and secondary analysis of effect sizes. Study selection: Clinical studies with a pre/post-intervention design and outcome measures for mood and depression as accepted in the S-3 guidelines (Association of Scientific Medical Societies in Germany). Data extraction: Study characteristics and outcomes (means and standard deviations) from participants receiving at least one WBH intervention. Results: A total of 7 studies and 148 subjects with a mean age of 46 years (36-56 years) were identified. Three out of seven studies utilized hot baths and 4/7 infrared heating. Study duration ranged from 1 to 6 weeks with one or multiple interventions and an average treatment time of 66.37 min (42.55-140). Risk of bias analysis revealed small sample biases and lack of control groups in 3/7 studies. About 21 study end-points were extracted with 19 resulting in effects sizes (Cohen's d) of 0.8 or greater. Target temperatures between 38 °C and 39 °C and slower increase in core body temperature during the intervention resulted in larger treatment effects. Conclusion: WBH is a promising alternative treatment for depression with low risk for adverse reactions and side effects but still lacking sufficient evidence for general recommendations for clinical practice. However, as all other interventions have failed, the studies to date can provide a framework for clinical application.

Patient involvement in comprehensive, complex cancer surgery: Perspectives of patients, relatives and health professionals.

We investigated the perspectives of patients, relatives and health professionals on the drivers and barriers to patient involvement (PI) in the treatment of peritoneal carcinomatosis with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). During 2016-2017, individual and focus group interviews were conducted with purposively selected participants during CRS and HIPEC, supplemented by field observations. This material was analysed using meaning condensation (Kvale). Fifteen patients, eight relatives and nine health professionals participated in 31 individual and two focus group interviews, supplemented by 37 observations. The findings were structured into themes concerning treatment decisions, organisation of pathways, knowledge of the patient and life during treatment. Deciding to treat was determined not only by preoperative biomedical information, personal preferences but also findings during surgery. This circumstance put the patients under mental pressure and affected their ability to process the offered information. They furthermore perceived the pathway as complex and occasionally unclear, leading them to attempt to coordinate transitions themselves. The study has highlighted barriers to, rather than drivers of, PI. To promote PI during comprehensive complex cancer surgery, we suggest that patients and relatives are offered patient-centred care, such as support in posing questions, overview of their treatment pathway and coherent transitions.

Role of Locoregional Therapy and Predictors for Dropout in Patients with Hepatocellular Carcinoma Listed for Liver Transplantation.

PURPOSE: To identify factors associated with removal from the liver transplantation waitlist because of death, deterioration of condition, or exceeding Milan criteria in patients with hepatocellular carcinoma (HCC), with emphasis on the role of locoregional therapy (LRT), defined as percutaneous thermal ablation and drug-eluting embolic chemoembolization, as bridge therapy. MATERIALS AND METHODS: All patients listed for liver transplant at a single institution with exception points for HCC during 2004-2012 were evaluated. The most common cause of cirrhosis was hepatitis C (68%; 121/177). Seventy-one percent (125/177) of patients underwent liver transplantation, and 83% (147/177) underwent at least 1 LRT procedure. Of the 52 patients who did not undergo liver transplantation, 31 (60%) of livers were removed because of progression of HCC. RESULTS: The likelihood of transplant was higher for patients who received LRT (odds ratio [OR], 2.9; confidence interval [CI], 2.2-7.2) and lower for patients with multifocal tumors (OR, 0.25; CI, 0.12-0.52) and with larger tumors (OR, 0.94; CI, 0.90-0.98). Time on the waitlist (OR, 0.99; CI, 0.99-1.0) was not found to correlate with removal. LRT increased the likelihood of liver transplantation, specifically for patients with prolonged wait times. Patients who demonstrated complete response (CR) to LRT on the first follow-up imaging study were more likely to undergo liver transplantation. CONCLUSIONS: LRT increased the likelihood of a patient with HCC achieving liver transplant, particularly in patients facing prolonged waiting times. CR after LRT significantly increased the likelihood of liver transplantation.

Quality of life in a phase 2 trial of short-course hyperthermic intraperitoneal chemotherapy (HIPEC) at interval debulking surgery for high tumor burden ovarian cancer.

INTRODUCTION: to evaluate the effect of short-course (i.e.: 30 minutes) HIPEC on health-related quality of life (HRQoL) in our feasibility study; NCT02249013. METHODS: a prespecified secondary end-point of our open-label, multicenter, single-arm, phase 2 trial on safety and efficacy was assessed using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30, version 3.0). Patients were required to complete the HRQoL questionnaire at baseline, after HIPEC, and after the end of the treatment. Changes of HRQoL over time were assessed by median scores for each domain and analyzed by Friedman`s test at a significant two-sided level of 0.05. RESULTS: fifteen patients with high tumor burden EOC were recruited from our public health system between February 2015 and July 2019. A baseline EORTC QLQ-C30 questionnaire and at least one follow-up questionnaire was received from all of the patients. No significant difference over time in the QLQC30 summary scores was observed (p>0.05). The transitory impairment on patients HRQoL immediately after the short-course HIPEC trended to return to baseline at the end of the multimodal treatment. CONCLUSIONS: we found no significant impairment of short-course HIPEC on patients HRQoL into the context of our comprehensive treatment protocol.

Warming the postpartum body as a form of postnatal care: An ethnographic study of medical injections and traditional health practices in Cambodia.

Postpartum care is a critical element for ensuring survival and health of mothers and newborns but is often inadequate in low- and middle-income countries due to barriers to access and resource constraints. Newly delivered mothers and their families often rely on traditional forms of postnatal care rooted in social and cultural customs or may blend modern and traditional forms of care. This ethnographic study sought to explore use of biomedical and traditional forms of postnatal care. Data were collected through unstructured observation and in-depth interviews with 15 mothers. Participants reported embracing traditional understandings of health and illness in the post-partum period centered on heating the body through diet, steaming, and other applications of heat, yet also seeking injections from private health care providers. Thematic analysis explored concepts related to transitioning forms of postnatal care, valuing of care through different lenses, and diverse sources of advice on postnatal care. Mothers also described concurrent use of both traditional medicine and biomedical postnatal care, and the importance of adhering to cultural traditions of postnatal care for future health. Maternal and newborn health are closely associated with postnatal care, so ensuring culturally appropriate and high-quality care must be an important priority for stakeholders including understand health practices that are evolving to include injections.

The long-term impact of hyperthermic intraperitoneal chemotherapy on survivors treated for peritoneal carcinomatosis: a cross-sectional study.

BACKGROUND: Hyperthermic intraperitoneal chemotherapy (HIPEC) after complete surgical resection is currently accepted as a therapeutic option for peritoneal carcinomatosis. However, considerable morbidity is reported after HIPEC. OBJECTIVE: We aimed to evaluate the impact of HIPEC on the quality of life (QoL) of survivors without recurrences of disease according to socio-demographic and medical variables. For that purpose, HIPEC was used as a global concept including the surgical procedure effects. MATERIALS AND METHODS: A cross-sectional study was performed by analyzing questionnaires concerning socio-demographic data, the psychological status, and general and specific QoL scores. RESULTS: Sixty-eight patients (86% of those contacted) completed and returned mailed questionnaires. For 19/21 QoL dimensions explored, survivors reported good to very good QoL with a median score >/=67%. The two adversely affected dimensions were future prospects and sexual functioning with a mean score of 57% and 23%, respectively. The burden of carcinomatosis, evaluated by a peritoneal index, was not correlated with statistically identified sequels in QoL. The extent of morbidity due to HIPEC, evaluated by the hospital stay, was statistically correlated with only one score, namely, embarrassment during social activities (p = 0.01) but not during familial life. CONCLUSIONS: Even though HIPEC is considered as an aggressive treatment, survivors reported good to very good QoL. However, specific care for the psychological aspect, as reflected by anxiety regarding future prospects and sexual activity, needs to be developed for survivors.

Psychological and systemic stress reactions of patients during hyperthermia treatments.

PURPOSE: This study evaluated psychological stress reactions during hyperthermia (HT) treatments and compared them to systemic stress reactions. MATERIALS AND METHODS: 27 patients with malignant disease were treated with superficial or regional hyperthermia. Cortisol and the catecholamines adrenaline and noradrenaline in venous blood were used as markers of psychological stress. The anxiety proneness of the patients was evaluated with a trait-anxiety inventory. Blood pressure and heart rate were markers of systemic stress. Patients were first grouped by superficial or regional treatment and then into two subgroups: anxious and non-anxious patients. RESULTS: The time course of the cortisol concentration of the superficial group showed a slight but significant decrease and that of the regional group an increase. The cortisol concentration of the regional group was sometimes slightly but significantly higher than in the superficial group, and in the group of anxious patients higher than in the group of non-anxious patients. The changes in time courses and differences in groups were not as pronounced for the catecholamine concentrations. Heart rate and blood pressure showed a significant increase only in the regional group, and there was no significant difference between the regional and the superficial groups. None of the variables showed a significant difference between the initial and the subsequent treatments; all lay well within the normal physiological range. CONCLUSIONS: These standard hyperthermia treatments are not excessively stressful, either systemically or psychologically. The different behaviours of the variables confirm that it makes sense to consider systemic stress as well as psychological reactions.

Meta-analysis of prognostic factors for patients with colorectal peritoneal metastasis undergoing cytoreductive surgery and heated intraperitoneal chemotherapy.

Background: Up to 15 per cent of colorectal cancers present with peritoneal metastases (CPM). Cytoreductive surgery and heated intraperitoneal chemotherapy (CRS + HIPEC) aims to achieve macroscopic tumour resection combined with HIPEC to destroy microscopic disease. CRS + HIPEC is a major operation with significant morbidity and effects on quality of life (QoL). Improving patient selection is crucial to maximize patient outcomes while minimizing morbidity and mortality. The aim of this study was to identify prognostic factors for patients with CPM undergoing CRS + HIPEC. Methods: A systematic search of MEDLINE, Embase and Cochrane Library electronic databases was performed using terms for colorectal cancer, peritoneal metastasis and CRS + HIPEC. Included studies focused on the impact of prognostic factors on overall survival following CRS + HIPEC in patients with CPM. Results: Twenty-four studies described 3128 patients. Obstruction or perforation of the primary tumour (hazard ratio (HR) 2·91, 95 per cent c.i. 1·5 to 5·65), extent of peritoneal metastasis as described by the Peritoneal Carcinomatosis Index (PCI) (per increase of 1 PCI point: HR 1·07, 1·02 to 1·12) and the completeness of cytoreduction (CC score above zero: HR 1·75, 1·18 to 2·59) were associated with reduced overall survival after CRS + HIPEC. Conclusion: Primary tumour obstruction or perforation, PCI score and CC score are valuable prognostic factors in the selection of patients with CPM for CRS + HIPEC.

Integrative Evaluation of Automated Massage Combined with Thermotherapy: Physical, Physiological, and Psychological Viewpoints.

Various types of massages are reported to relieve stress, pain, and anxiety which are beneficial for rehabilitation; however, more comprehensive studies are needed to understand the mechanism of massage therapy. In this study, we investigated the effect of massage therapy, alone or in combination with infrared heating, on 3 different aspects: physical, physiological, and psychological. Twenty-eight healthy university students were subjected to 3 different treatment conditions on separate days, one condition per day: control, massage only, or massage with infrared heating. Physical (trunk extension [TE]; maximum power of erector spinae), physiological (heart-rate variability [HRV]; electroencephalogram [EEG]), and psychological (state-trait anxiety inventory [STAI]; visual analogue scale [VAS]) measurements were evaluated and recorded before and after each treatment condition. The results showed that massage therapy, especially when combined with infrared heating, significantly improved physical functioning, increased parasympathetic response, and decreased psychological stress and anxiety. In the current study, we observed that massage therapy contributes to various physical, physiological, and psychological changes, where the effect increases with thermotherapy.

[Qualitative and collaborative research with cancer patients. Experience narratives of treatments for peritoneal carcinomatosis]. / Une recherche qualitative et collaborative auprès de patients atteints de cancer. Récits d'expérience des traitements de la carcinose péritonéale.

UNLABELLED: This CORCAN study is concerned with the way patients hospitalised for peritoneal carcinosis perceive surgical treatment and hyperthermic intraperitoneal chemotherapy (HIPEC). OBJECTIVES: (1) To identify and analyse, using concepts of social representation and accounts of the illness, characteristics of the way this treatment is experienced; (2) to inform doctors and healthcare workers about patients' representations, with a view to adjusting the treatment, the care and the information given to patients. METHODOLOGY: Fifty-eight directive and nondirective interviews were conducted longitudinally with 21 patients (13 women and 7 men) hospitalised for treatment by cell killing and HIPEC. RESULTS: Five important elements of concern were raised and discussed by the patients at different stages of the disease, then reported and discussed with the doctors and healthcare workers. These were patients' experiences of: the hyperthermic intraperitoneal chemotherapy (HIPEC), randomisation, intensive care, the effects of surgery on the digestive system, reorganising their diet, and returning home.

Quality of life in a phase 2 trial of short-course hyperthermic intraperitoneal chemotherapy (HIPEC) at interval debulking surgery for high tumor burden ovarian cancer / Avaliação da qualidade de vida em ensaio clínico de fase 2 envolvendo quimioterapia intraperitoneal hipertérmica (HIPEC) de curta duração no momento da citorredução de intervalo em pacientes com câncer de ovário de grande volume tumoral

ABSTRACT Introduction: to evaluate the effect of short-course (i.e.: 30 minutes) HIPEC on health-related quality of life (HRQoL) in our feasibility study; NCT02249013. Methods: a prespecified secondary end-point of our open-label, multicenter, single-arm, phase 2 trial on safety and efficacy was assessed using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30, version 3.0). Patients were required to complete the HRQoL questionnaire at baseline, after HIPEC, and after the end of the treatment. Changes of HRQoL over time were assessed by median scores for each domain and analyzed by Friedman`s test at a significant two-sided level of 0.05. Results: fifteen patients with high tumor burden EOC were recruited from our public health system between February 2015 and July 2019. A baseline EORTC QLQ-C30 questionnaire and at least one follow-up questionnaire was received from all of the patients. No significant difference over time in the QLQC30 summary scores was observed (p>0.05). The transitory impairment on patients HRQoL immediately after the short-course HIPEC trended to return to baseline at the end of the multimodal treatment. Conclusions: we found no significant impairment of short-course HIPEC on patients HRQoL into the context of our comprehensive treatment protocol.

RESUMO Objetivo: avaliar o impacto da quimioterapia intraperitoneal hipertérmica (HIPEC) de curta duração (i.e.: 30 minutos) na qualidade de vida (QoL) relacionada à saúde (HRQoL) no contexto de ensaio clínico terapêutico piloto; NCT02249013. Métodos: avaliou-se o desfecho secundário predeterminado de HRQoL em ensaio clínico de fase 2 de segurança e eficácia, aberto, multicêntrico, de braço único, utilizando-se o questionário European Organization for Research and Treatment of Cancer Quality of Life (EORTC QLQ-C30, versão 3.0). As pacientes foram solicitadas a responder o questionário de HRQoL antes do tratamento, após a HIPEC, e ao fim do tratamento interdisciplinar. As variações da HRQoL ao longo do tempo foram avaliadas pelas medianas dos escores de cada domínio e analisadas pelo teste de Friedman, considerando-se nível de significância estatística bicaudal de 5%. Resultados: quinze pacientes com câncer de ovário de grande volume tumoral foram recrutadas do sistema de saúde pública (i.e.: SUS) entre fevereiro de 2015 e julho 2019. Um questionário basal e pelo menos um questionário de acompanhamento foram coletados de todas as pacientes. Não se observou diferença significativa ao longo do tempo na HRQoL em nenhum dos domínios ou sintomas estudados (p> 0,05). O comprometimento transitório da HRQoL imediatamente após a HIPEC de curta duração tendeu a retornar à linha de base ao final do tratamento multimodal. Conclusões: não se observou impacto significativo da HIPEC de curta duração sobre a HRQoL no contexto deste protocolo de tratamento interdisciplinar.

The role of interleukin-6 in stress-induced hyperthermia and emotional behaviour in mice.

Psychological stress influences behaviour as well as autonomic functions such as body temperature. The mechanism that induces hyperthermia during stress is unknown. A recent hypothesis suggests that interleukin-6 (IL-6), an endogenous pyrogen, elevates body temperature during stress. To investigate the role of IL-6 during stress, we measured mRNA levels of IL-6 by quantitative PCR in various tissues 60 min after exposure of mice to open field stress. IL-6 mRNA was elevated in the hypothalamus three-fold and in the pituitary two-fold. However, there was no difference between the increase in body temperature after exposure to 60 min open field stress in wild-type controls (35.2+/-0.6-37.3+/-0.5 degrees C) and IL-6-deficient animals (34.8+/-0.4-37.0+/-0.3 degrees C). In contrast to body temperature, emotional behaviour differed between wild-type controls and IL-6-deficient mice. IL-6-deficient animals showed higher locomotor activity in an open field and lower levels of exploration of the open arms of the elevated plus maze than control animals. These data suggest that IL-6 plays an important role in the control of emotionality, but not in the regulation of body temperature after psychological stress.

Adult siRNA-induced knockdown of mGlu7 receptors reduces anxiety in the mouse.

Our knowledge regarding the molecular pathophysiology underlying anxiety disorders remains incomplete. Increasing evidence points to a role of glutamate in anxiety. The group III metabotropic glutamate receptors (mGlu4, mGlu6, mGlu7 and mGlu8 receptors) remain the least investigated glutamate receptor subtypes partially due to a delay in the development of specific pharmacological tools. Early work using knockout animals and pharmacological tools aimed at investigating the role of mGlu7 receptor in the pathophysiology of anxiety disorders has yielded exciting yet not always consistent results. To further investigate the role this receptor plays in anxiety-like behaviour, we knocked down mGlu7 receptor mRNA levels in the adult mouse brain using siRNA delivered via an osmotic minipump. This reduced anxiety-like behaviour in the light-dark box coupled with an attenuation of stress-induced hyperthermia (SIH) and a reduction of the acoustic startle response (ASRs) in the fear-potentiated startle paradigm (FPS). These effects on anxiety-like behaviour were independent of any impairment of locomotor activity and surprisingly, no behavioural changes were observed in the forced swim test (FST), which is in contrast to mGlu7 receptor knockout animals. Furthermore, the previously reported epilepsy-prone phenotype seen in mGlu7 receptor knockout animals was not observed following siRNA-induced knockdown of the receptor. These data suggest targeting mGlu7 receptors with selective antagonist drugs may be an effective and safe strategy for the treatment of anxiety disorders.

Effects of stone spa (Ganban-yoku) on psychological states.

This uncontrolled intervention study explored the effects of stone spa use on the psychological states of women. Sixty-eight female volunteers (mean age 37.5 years (standard deviation 14.8)) recruited at a women-only stone spa facility participated in the study. They completed the short-form Profile of Moods States (POMS) and the State-Trait Anxiety Inventory (STAI) before and after stone spa use in order to determine changes in mood and anxiety states. Six factors relating to mood were measured using the POMS: Tension-Anxiety, Depression-Dejection, Anger-Hostility, Vigor, Fatigue, and Confusion. The two anxiety concepts of state anxiety and trait anxiety were also measured. The scores for Tension-Anxiety and Anger-Hostility and both anxiety measures were improved statistically after stone spa use. Stone spa use shows considerable promise for improving mood and reducing anxiety. Since this study was a descriptive, prospective and uncontrolled intervention study, further investigation of these promising findings is warranted.

Febrile convulsions in developing rats induce a hyperanxious phenotype later in life.

Exposure of rodent pups to hyperthermia constitutes one of the best known models of febrile seizures. Studies designed to evaluate the behavioral impact of heat-induced convulsions (HCs) have focused mainly on hippocampus-dependent tasks and produced rather conflicting results. In this study, we assessed, in detail, developmental milestones, emotional behavior, and cognitive performance in animals submitted to HCs on Postnatal Day 10. There was no alteration in the acquisition of neurological reflexes, but there was an anticipation of eye opening in animals exposed to hyperthermia. As adults, the locomotor and exploratory behavior of these rats was unaffected. Interestingly, animals exposed to hyperthermia displayed signs of increased anxiety in the elevated-plus maze, although these signs were not associated with increased susceptibility to depression-like behavior. Additionally, we failed to observe impairments in spatial and working memory tasks. In conclusion, HCs at a particular period of neurodevelopment determine a hyperanxious phenotype later in life.

Changes in mood state following whole-body hyperthermia.

Mood states of cancer patients were assessed pre- and post-41.8 degrees C whole-body hyperthermia using the Profile of Mood States questionnaire. Results demonstrated a statistically significant increase in fatigue associated with decreased vigour which returned to baseline values by 72 h. In contrast, a significant improvement in depression was evident through 72 h following treatment. The relationship of this result to earlier studies of WBH-induced beta-endorphin is discussed.