Nutritional interventions during treatment for ovarian cancer: A narrative review and recommendations for future research.

Most women with ovarian cancer are diagnosed at an advanced stage (stage III or IV), when the intraabdominal spread of the tumour impacts nutrient intake and absorption. Up to 70 % of women with ovarian cancer are malnourished and approximately 40 % are affected by muscle loss at the time of diagnosis. Women with ovarian cancer are at high risk of nutritional decline due to invasive treatment and the severity of side-effects. This review explores the evidence evaluating nutritional interventions during treatment for ovarian cancer and their effect on nutritional status, muscle mass, and clinical outcomes. Perioperative immunonutrition has been investigated with mixed results for immediate postoperative outcomes. Individualised nutrition counselling as part of a multimodal prehabilitation programme prior to surgery shows promising results; however, the effects are limited by sample size. Nutrition counselling as part of a mixed intervention with exercise shows high acceptability and suggests improvements in dietary intake and quality of life during chemotherapy treatment, while oral nutritional supplements and nutrition education appear to reduce symptom burden. Individualised nutrition counselling during treatment also appears to be associated with improved overall survival; however, the evidence is limited to a single retrospective study. A key finding from this review is that, despite the high prevalence of malnutrition and muscle loss in women with ovarian cancer and the critical importance of addressing these modifiable prognostic factors, nutrition intervention studies are limited. Prospective studies with samples large enough to provide adequate power to evaluate intervention effectiveness are urgently required to inform optimal management.

Effect of virtual reality-based mindfulness training model on anxiety, depression, and cancer-related fatigue in ovarian cancer patients during chemotherapy.

BACKGROUND: Although the prognosis of ovarian cancer can be significantly improved through standardized surgery and chemotherapy, 70% of epithelial ovarian cancer (EOC) patients would suffer from drug resistance and recurrence during the long chemotherapy cycle. OBJECTIVE: To explore the impact of a training mode based on the integration of virtual reality technology and mindfulness on anxiety, depression, and cancer-related fatigue in ovarian cancer patients during chemotherapy. METHOD: Through virtual reality technology, a mindfulness training software was designed and developed, and a mindfulness training mode based on virtual reality technology was constructed. Using a self-controlled design, 48 ovarian cancer patients undergoing chemotherapy who were hospitalized in a tertiary hospital in Beijing from August 2022 to May 2023 were conveniently selected as the research subjects. The patients were subjected to four weeks of mindfulness training based on virtual reality technology, and the acceptance of the mindfulness training mode using virtual reality technology was evaluated. The Hospital Anxiety and Depression Scale (HADS) and Cancer Related Fatigue Scale (CRF) were used to evaluate the anxiety, depression, and fatigue of patients before and after intervention. RESULTS: The virtual reality based mindfulness training mode includes four functional modules: personalized curriculum, intelligent monitoring, emotion tracking, and Funny Games. 48 patients had a high acceptance score (139.21 ± 10.47), and after using mindfulness training mode based on virtual reality technology, anxiety, depression, and cancer-related fatigue in ovarian cancer patients during chemotherapy were significantly reduced, with a statistically significant difference (p< 0.001). CONCLUSION: Ovarian cancer patients during chemotherapy have a high acceptance of virtual reality based mindfulness training mode. The application of this mode can reduce the psychological problems of anxiety, depression, and cancer-related fatigue in ovarian cancer patients during chemotherapy, and is worth promoting and using.

Cardiac safety analysis of first-line chemotherapy drug pegylated liposomal doxorubicin in ovarian cancer.

Pegylated liposomal doxorubicin (PLD) is a nano-doxorubicin anticancer agent. It was used as early as 2014 to treat ovarian and breast cancer, multiple myeloma and Kaposi's sarcoma. The 2018 National Comprehensive Cancer Network guidelines listed PLD as first-line chemotherapy for ovarian cancer. PLD has significant anticancer efficacy and good tolerance. Although PLD significantly reduces the cardiotoxicity of conventional doxorubicin, its cumulative-dose cardiotoxicity remains a clinical concern. This study summarizes the high-risk factors for PLD-induced cardiotoxicity, clinical dose thresholds, and cardiac function testing modalities. For patients with advanced, refractory, and recurrent malignant tumors, the use of PLD is still one of the most effective strategies in the absence of evidence of high risk such as cardiac dysfunction, and the lifetime treatment dose should be unlimited. Of course, they should also be comprehensively evaluated in combination with the high-risk factors of the patients themselves and indicators of cardiac function. This review can help guide better clinical use of PLD.

CT Imaging Findings in Patients with Ovarian Cancer and Acute Abdominal Symptoms: Experience at a Tertiary Cancer Center.

PURPOSE: To evaluate computed tomography (CT) findings in patients with ovarian cancer presenting to a comprehensive cancer center's urgent care unit with acute abdominal symptoms. METHODS: This retrospective study included consecutive patients with ovarian cancer who underwent abdominal CT at a comprehensive cancer center's urgent care unit between January 1, 2018, and January 14, 2020, due to acute abdominal symptoms. Two abdominal radiologists reviewed the abdominal CT reports, categorizing imaging findings as follows: (a) no new or acute finding, (b) new or increased bowel or gastric obstruction, (c) new or increased ascites, (d) new or increased peritoneal carcinomatosis, (e) new or increased nonperitoneal metastases, (f) new inflammatory or infectious changes, (g) new or increased hydronephrosis, (h) new or increased biliary dilatation, (i) new vascular complications, or (j) new bowel perforation. RESULTS: A total of 200 patients (mean age, 59 years; range, 22-87) underwent a total of 259 abdominal CT scans, of which 217/259 (83.8%) scans were found to have new or increased findings. A total of 115/259 (44.4%) scans had only one finding while 102/259 (39.4%) scans had 2 or more findings. Altogether, 382 new or increased findings were detected: findings were most commonly related to bowel or gastric obstruction (92/382, 24.1%) with small bowel obstruction being the most common finding (80/382, 20.9%); ascites (78/382, 20.4%); peritoneal carcinomatosis (62/382, 16.2%); and nonperitoneal metastases (62/382, 16.2%). Inflammatory or infectious findings accounted for 30/382 (7.9%) findings. CONCLUSION: Most patients with ovarian cancer presenting with acute abdominal had relevant positive findings on abdominal CT, with small bowel obstruction being the most common finding.

Hyperthermic intrathoracic chemotherapy for the treatment of malignant pleural effusion caused by breast and ovarian cancer: A systematic literature review and pooled analysis.

OBJECTIVES: Breast and ovarian cancer account for over 30% of malignant pleural effusions (MPEs). Treatment of the metastatic disease requires control of the MPE. Even though primarily symptomatic, the treatment of the MPE can potentially affect the oncological course of the disease. The aim of this review is to analyze the effectiveness of intrathoracic chemotherapy in the treatment of MPE caused by breast and ovarian cancer. METHODS: A systematic literature research was conducted up until May 2021. Studies published in English on patients undergoing either surgical or interventional intrapleural chemotherapy were included. RESULTS: Thirteen studies with a total of 497 patients were included. Analysis was performed on 169 patients with MPE due to breast cancer and eight patients with MPE secondary to ovarian cancer. The pooled success rates of intrathoracic chemotherapy for controlling the MPE were 59.1% and 87.5%, respectively. A survival analysis was not possible with the available data. The overall toxicity of the treatment was low. CONCLUSIONS: Intrathoracic chemotherapy achieves symptomatic control of the MPE in 59.1% of patients with metastatic breast cancer and 87.5% of patients with metastatic ovarian cancer. This is inferior to other forms of surgical pleurodesis. Data from small case series and studies on intraperitoneal chemotherapy show promising results. However, formal oncological studies on the use of intrathoracic chemotherapy for metastatic breast or ovarian cancer are lacking. Further prospective pilot studies are needed to assess the therapeutic oncological effects of this treatment.

Nurse-led exercise and cognitive-behavioral care against nurse-led usual care between and after chemotherapy cycles in Han Chinese women of ovarian cancer with moderate to severe levels of cancer-related fatigue: A retrospective analysis of the effectiveness.

ABSTRACT: Women with ovarian cancer are reported to fatigue over time. Moderate to severe levels of cancer-related fatigue is fluent in Han Chinese patients with cancer. Comprehensive Cancer Network guidelines are recommending exercise and cognitive behavioral therapy to reduce cancer-related fatigue. Exercise is an easy, cost-effective, and non-pharmacological approach. The objective of the study was to evaluate the effectiveness of nurse-led exercise and cognitive-behavioral care against nurse-led usual care in Han Chinese women of ovarian cancer regarding cancer-related fatigue, depressive symptoms, and sleep quality.Han Chinese women with moderate to severe levels of cancer-related fatigue have received 30 minutes, 5 times/week nurse-led exercise and 60 min/week cognitive-behavioral care (EC cohort, n = 118) or nurse-led usual care regarding educations and recommendations only (UC cohort, n = 126) or have not received nurse-led exercise, cognitive-behavioral care, educations, and recommendations (NC cohort, n = 145) between and after chemotherapy cycles. The Piper Fatigue Scale, the Zung Self-rating Depression Scale, and Pittsburgh Sleep Quality Index questionnaires were evaluated at the start and the end of non-pharmacological treatment.At the end of treatment as compared to the start of treatment, only women of EC cohort had decrease Piper Fatigue Scale (5.40 ±â€Š1.49/woman vs 6.06 ±â€Š1.49/woman, P < .0001, q = 4.973) and Zung Self-rating Depression Scale score (48.67 ±â€Š4.24/woman vs 49.93 ±â€Š4.29/woman, P = .001, q = 3.449). Also, at the end of treatment, as compared to the start of treatment, only women of EC cohort have increased Pittsburgh Sleep Quality Index score (14.76 ±â€Š2.18/woman vs 13.94 ±â€Š2.90/woman, P = .045, q = 3.523). Only exercise and cognitive-behavioral care were successful in a decrease in the numbers of women with depression (the Mandarin Chinese version of the Zung Self-rating Depression Scale score >53, 32 vs 16, P = .015).Nurse-led exercise and cognitive-behavioral care can help Han Chinese women with ovarian cancer to decrease cancer-related fatigue and depression. Also, it can improve the quality of sleep.Evidence Level: 4.Technical Efficacy: Stage 5.

Ovarian Leydig cell tumor and postmenopausal hirsutism with signs of virilisation.

A 71-year-old woman was referred to the endocrinology clinic to investigate postmenopausal hirsutism with 10 years of evolution. She had history of regular menses and menopause with 50 years old. Physical examination showed a male pattern facies, deepening of the voice, androgenic alopecia and hirsutism with a score of 23 according to the modified Ferriman-Gallwey scale. Testosterone and androstenedione were increased. Transvaginal ultrasound, abdominal and pelvic CT showed uterine fibroids with no pathological findings in the adrenals or ovaries. Since she had postmenopausal vaginal bleeding, uterine fibroids and suspicion of an ovarian source for her hyperandrogenism, total hysterectomy and bilateral oophorectomy were performed. Histopathological diagnosis was a Leydig cell tumour located in left ovary and endometrial carcinoma. Improvement of hirsutism was started to notice 1 month after the surgery and she was referred to the oncology clinic for adjuvant treatment.

[HIPEC in ovarian cancer: What should we expect?] / CHIP et cancers de l'ovaire : pour quelles patientes ?

The results of PRODIGE 7 study demonstrate that the use of HIPEC is not beneficial for patients in the treatment of colorectal carcinomatosis. Nevertheless, a recent study published in NewEnglandJournalofMedicine showed that hyperthermic intraperitoneal chemotherapy (HIPEC) increased overall survival for patients with ovarian peritoneal carcinomatosis. Although, the emergence of targeted therapies (anti-angiogenic agents, PARP-inhibitors, anti-PDL1) results in new standards of treatment in first line or recurrence disease. In this general context, what is the potential interest of HIPEC for the treatment of ovarian carcinoma?

Polypharmacy in Patients with Ovarian Cancer.

OBJECTIVE: Polypharmacy has been associated with morbidity and mortality in patients with cancer. Data about polypharmacy among patients with ovarian cancer are limited. The primary objective of this study was to evaluate polypharmacy in a cohort of patients with ovarian cancer and to assess the evolution of polypharmacy from initial presentation to 2 years posttreatment. A secondary objective was to evaluate differences in polypharmacy between a subset of patients primarily treated in our comprehensive cancer center (CCC) and our safety net hospital (SNH). METHODS: Women treated for ovarian cancer between January 1, 2011, and December 31, 2016, were included. Data were abstracted from the electronic medical record. Medication safety was assessed using the established Anticholinergic Burden (ACB) scale and the Beers criteria. Statistical analyses were performed using paired t tests and Cox proportional hazards models, with significance set at p < .05. RESULTS: The study included 152 patients. The majority of patients had high-grade serous carcinoma. Hypertension was the most common medical problem. The mean number of medications at the time of diagnosis was 3.72. Paired testing demonstrated significant patient-level increases in the number medications at 2 years following initial diagnosis (4.16 vs. 7.01, p < .001). At the CCC, 47.4% of patients met criteria for polypharmacy at diagnosis compared with 19.4% at the SNH (p < .001). By 2 years postdiagnosis, 77.6% of patients at the CCC met criteria for polypharmacy compared with 43.3% at the SNH (p = .001). The use of any medications on the ACB scale (p < .001) increased significantly between initial diagnosis and 2 years for the entire population. Polypharmacy was not a significant predictor of overall survival. CONCLUSION: Polypharmacy worsens as women go through ovarian cancer treatment. Both at initial presentation and at 2 years postdiagnosis, rates of polypharmacy were higher at the CCC. Polypharmacy did not have an effect on survival in this cohort. IMPLICATIONS FOR PRACTICE: Awareness of escalating numbers of medications and potentially adverse interactions is crucial among women with ovarian cancer, who are at high risk for polypharmacy.

Pilot randomized controlled trial of auricular point acupressure for sleep disturbances in women with ovarian cancer.

Sleep disturbance is a significant problem affecting around 50% of cancer patients. Non-pharmacological interventions can be used to improve sleep quality in cancer patients, but little is known about the feasibility, acceptability, and effectiveness of auricular point acupressure (APA) to reduce sleep disturbance in women with ovarian cancer undergoing chemotherapy. A pilot randomized controlled trial was conducted at a publicly funded hospital in southern Taiwan. Fifty-five eligible women were approached and 47 women participated. Women randomly assigned to the control group (n = 24) received sleep hygiene practices alone. Women in the intervention group (n = 23) received sleep hygiene practices and APA treatment which involved gentle fingertip pressure at acupoints on the external ear. The Pittsburgh Sleep Quality Index (PSQI) was completed at four time points. Forty women completed the trial giving a retention rate of 85%. Women receiving the intervention reported a 65% reduction in sleep disturbance according to PSQI global scores from Time 1 (mean = 13.2) to Time 2 (mean = 4.65) after 4 weeks of APA treatment. There was a further 10% decrease in PSQI scores at Time 3 (mean = 4.21) after 6 weeks of APA treatment. Compared to controls, women receiving APA had significantly lower PSQI mean global scores at both Time 2 and Time 3 (p < .001). APA treatment for women with ovarian cancer produced significantly improved sleep. Participants found the procedure easy to perform. Pilot findings support the feasibility of a longitudinal study with a larger, representative sample.

Peri-operative oral immunonutrition in malnourished ovarian cancer patients assessed by the nutritional risk screening.

OBJECTIVES: Aim of this study was to determine whether peri-operative immunonutrition can decrease complications and the length of stay (LOS) in malnourished ovarian cancer patients. STUDY DESIGN: Patients suspicious for advanced ovarian cancer before histopathological diagnosis and a nutritional risk score (NRS) ≥ 3 received oral immune-modulating diets (IMDs) for 5 days pre-operative and at least 5 days post-operative. Parameters for clinical outcome were infectious and non-infectious complications during hospital stay, and time of hospitalization. The results were compared with malnourished ovarian cancer patients of a previous study without any additive nutritional support (standard clinical diet/nutrition). RESULTS: The infectious and non-infectious complication rate in the interventional group (IG) N = 28 was 42.9%, similar to the control group (CG) N = 19 with 42.1%, whereas the rate of infectious complications in the IG (21.4%) was slightly lower compared to the CG (26.3%). The median LOS of the IG was 18 days, and therefore, longer than LOS of the CG (15 days). Regarding the patients' compliance pre-operative 78.6% of the patients took the IMDs in an optimal and sufficient amount. Whereas after surgery, only eight (28.6%) patients were able to take IMDs in optimal and sufficient amount. CONCLUSIONS: The current study showed no improvement of the complication rate or the time of hospitalization due to additional peri-operative immunonutrition in malnourished ovarian cancer patients. However, a trend towards the reduction of infectious complications could be seen in the IG.

Ascitic fluid from advanced ovarian cancer patients compromises the activity of receptor tyrosine kinase inhibitors in 3D cell clusters of ovarian cancer cells.

Ovarian cancer patients in the advanced stages of the disease show clinical ascites, which is associated with a poor prognosis. There is limited understanding of the effect of ascitic fluid on ovarian cancer cells and their response to anticancer drugs. We investigated the antitumour effects of EGFR/Her-2 (canertinib) and c-Met (PHA665752) inhibitors in a 3D cell model of three ovarian cancer lines. Single and combined inhibitor treatments affected cell growth of OVCAR-5 and SKOV-3 cell lines but not OV-90 cell line. Growth reduction was correlated with the down expression of PCNA, EGFR, HER-2, c-MET, ERK and AKT and their phosphorylation status in cells in growth factor supplemented media. However, these effects were not re-producible in OVCAR-5 and SKOV-3 cell lines when they were exposed to ascitic fluid obtained from three ovarian cancer patients. Serum albumin and protein components in the ascitic fluids may reduce the cellular uptake of the inhibitors.

Hyperthermic Intraperitoneal Perfusion Chemotherapy and Cytoreductive Surgery for Controlling Malignant Ascites From Ovarian Cancer.

BACKGROUND: Malignant ascites, a complication often seen in patients with ovarian cancer (OC), is difficult to treat, but hyperthermic intraperitoneal chemotherapy (HIPEC) has a good efficacy. OBJECTIVE: The aim of this study was to assess the efficacy of cytoreductive surgery (CRS) combined with HIPEC for controlling malignant ascites from OC. MATERIALS AND METHODS: From December 2009 until December 2014, 53 patients with OC and malignant ascites were treated with CRS and HIPEC. Patients in good health condition were treated with CRS followed by HIPEC (CRS + HIPEC), and patients in poor health condition were treated initially with B-mode ultrasound-guided HIPEC followed by delayed CRS upon improvement of their health condition (HIPEC + delayed CRS). Resolution of ascites, complete CRS, overall survival, and disease-free survival were analyzed. RESULTS: All patients showed ascites regression. The total objective remission rate was 100%, even for patients in the poor condition group before CRS. Complete CRS was successful in 30 (88.23%) of 34 patients in the good condition group, and 17 (89.47%) of 19 patients in the poor condition group (P > 0.05). Median disease-free survival and median overall survival were 21 and 39 months in the good condition group, and 22 and 38 months in the poor condition group, respectively (P > 0.05). CONCLUSIONS: Hyperthermic intraperitoneal chemotherapy is effective at controlling ascites in patients with OC, even for patients in poor condition before CRS, or when complete CRS is not feasible. Furthermore, the regression of ascites appears not to be dependent on complete resection.

Multimodal oncosurgery approach to treat peritoneal carcinomatosis in a patient with occlusive ovarian carcinoma.

UNLABELLED: Summary BACKGROUND: This paper aims to present a "pattern" of oncosurgery solution in a case generally considered unrecoverable: intestinal occlusion in case of ovarian carcinoma and carcinomatosis. CASE REPORT: A 62-year-old female patient with ascites, carcinomatosis, unresectable pelvic tumour, and intestinal obstruction suffered a five-step oncosurgery "model": three surgical interventions overlapping chemotherapy administered via the systemic and intraperitoneal route: Step 1: colostomy and partial omentectomy; Step 2: five courses of systemic chemotherapy supported by granulocyte colony-stimulating factor; Step 3: radical surgery--total hysterectomy, bilateral adnexectomy, pelvic lymphadenectomy, omentectomy, appendectomy, pelvic peritonectomy, and hyperthermic intraperitoneal chemotherapy; Step 4: consolidation systemic chemotherapy consisting of three more similar cycles; Step 5: closure of the colostomy. Nine months after the beginning of treatment, the patient is with no evidence of disease. CONCLUSIONS: The association of surgical and oncologic treatment and the use of hyperthermic intraperitoneal chemotherapy (HIPEC) technology can solve some of these complex cases.

Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) in pediatric ovarian tumors: a novel treatment approach.

PURPOSE: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) have been used in adults with ovarian carcinoma proving overall survival benefit in randomized trials, but measured in months. Diffuse peritoneal disease from pediatric type ovarian tumors is rare. We applied CRS and HIPEC to pediatric girls with diffuse peritoneal disease as part of a clinical trial. METHODS: In all patients complete cytoreduction was followed by HIPEC using 100 mg/m2 of cisplatin for 90 min in a closed technique. All received neoadjuvant chemotherapy. Patients with disease outside of the abdominal cavity were excluded. RESULTS: Of 101 pediatric CRS and HIPEC operations, 8 had ovarian primary tumors and multifocal peritoneal disease. There were three yolk sac tumors (germ cell, mixed teratoma), one Sertoli­Leydig, one PNET of the ovary, one choriocarcinoma, one juvenile granulosa cell tumor and one adenocarcinoma. Age ranged 4­18 years. Three of the 8 (37 %) recurred and died. The remaining 63 % are disease free 2­6 years post HIPEC. Overall survival and relapse-free survival in this cohort was 64 and 62 %, respectively [CI 0.64 (0.34, 1); 0.62 (0.37, 1)]. CONCLUSIONS: This is the first report of CRS and HIPEC in pediatric ovarian tumors. HIPEC may be effective in pediatric-type ovarian tumors. More study is needed in a larger cohort.

Vitamin D supplementation review and recommendations for women diagnosed with breast or ovary cancer in the context of bone health and cancer prognosis/risk.

Vitamin D review and supplementation recommendations for women diagnosed with breast or ovary cancer have been defined in the context of bone health and cancer prognosis/risk taking as reference wider cancer patients and postmenopausal women. This specific group has been selected due to its higher osteoporosis risk versus postmenopausal women. Early vitamin D supplementation could help maintain bone health, as well as potentially enhance cancer survival rate. Factors considered for supplementation include daily dose, periodicity, chemical form, administration, and serum levels. Sufficient vitamin D serum levels are recommended to be above 30 ng/ml (75 nmol/l). Maintenance oral supplementation equivalent to a minimum daily dosage of 800-1000 IU (20-25 µg) cholecalciferol provided in a daily to monthly bases is preferred, also advised to start with higher dosages when vitamin D serum levels are <10 ng/ml (25 nmol/l). Calcidiol supplementation is more effective, making it advantageous for cases with very low or difficult to raise vitamin D serum levels.

Risk of ischemic stroke in patients with ovarian cancer: a nationwide population-based study.

BACKGROUND: Cancer patients are at risk of thromboembolism. However, studies investigating the relationship between ovarian cancer and ischemic stroke are lacking. The objectives of this study were to assess the association between ovarian cancer and ischemic stroke, and to determine the predictive risk factors. METHODS: Ovarian cancer patients aged 20 years and older without antecedent cerebrovascular events and who were followed up for more than 1 year between 1 January 2003 and 31 December 2011 were recruited from the Taiwan National Health Insurance database. Hazard ratios (HRs) of stroke risk for ovarian cancer patients compared with an age- and comorbidity-matched cohort were calculated by Cox proportional regression analysis. The difference in cumulative ischemic stroke incidence between ovarian cancer patients and the matched cohort was analyzed with the Kaplan-Meier method and tested with the log-rank test. RESULTS: Each cohort (ovarian cancer and matched cohort) consisted of 8,810 individuals, with a median age of 49 years. After a median follow-up of 2.68 and 3.85 years, respectively, the ischemic stroke incidence was 1.38-fold higher in the ovarian cancer cohort than in the comparison cohort (9.4 versus 6.8 per 1,000 person-years), with an age- and comorbidity-adjusted HR of 1.49 (P <0.001). The ischemic stroke risk imposed by ovarian cancer was more prominent in patients under 50 years old (HR 2.28; P <0.001) compared with patients 50 years and older (HR 1.33; P = 0.005). Significant risk factors predicting stroke development were age 50 years and older (HR 2.21; P <0.001), hypertension (HR 1.84; P <0.001), diabetes mellitus (HR 1.71; P <0.001), and treatment with chemotherapy (HR 1.45; P = 0.017), especially platinum-based regimens. CONCLUSIONS: Ovarian cancer patients were at an increased risk of developing ischemic stroke. Age, hypertension, diabetes, and chemotherapy treatment were independent risk factors.

Denosumab should be the treatment of choice for bisphosphonate refractory hypercalcaemia of malignancy.

Denosumab, a fully humanised monoclonal antibody, is licensed for treatment of postmenopausal osteoporosis, hormone ablation-induced bone loss and for prevention of skeleton-related events in patients with bone metastases from solid tumours. In pivotal phase 3 randomised trials, denosumab caused profound hypocalcaemia in patients with normocalcaemia despite oral calcium and vitamin D supplementation. This significant hypocalcaemic effect can be exploited to treat hypercalcaemia of malignancy (HCM). Recent reports from the USA suggest that denosumab is an effective treatment of HCM. According to our knowledge, we report the first two cases in UK with bisphosphonate refractory hypercalcaemia who responded to denosumab injections. Our first case gained 7 months of stabilisation of hypercalcaemia following prolonged admissions with life-threatening levels, while our second case achieved rapid normalisation of serum calcium levels for the first time in 14 months. We conclude that denosumab should be the treatment of choice for patients with bisphosphonate refractory hypercalcaemia.