Effects of an early intervention with Hyperbaric Oxygen Treatment on arm lymphedema and quality of life after breast cancer-an explorative clinical trial.

PURPOSE: Lymphedema (LE) is a common complication after breast cancer treatment, which negatively affects the quality of life (QOL). Hyperbaric Oxygen Treatment (HBOT) is an established treatment for radiation-induced tissue injury, but evidence of effect on breast cancer-related LE is inconclusive. We aimed to explore effects of HBOT on early breast cancer-related LE and the implications for QOL. METHODS: We invited women with breast cancer treated with surgery, axillary dissection and radiotherapy, who had participated in a randomized controlled trial and who presented with LE 1 year after surgery. In a prospective observational study design, change in LE was assessed with perometry, dual-energy X-ray absorptiometry (DXA) and lymphoscintigraphy, and QOL by validated self-report scales. Participants were offered 40 sessions of HBOT on every weekday for 8 weeks and were followed for 6 months. RESULTS: Out of 50 eligible participants, 20 women accepted participation. Nineteen women initiated and completed treatment and follow-up. None of the objective measures of LE severity showed consistent changes during the study period, but participants reported significant improvements in QOL (physical functioning, fatigue, insomnia and breast and arm symptoms), with improvements peaking at 6-month follow-up. CONCLUSION: Participants receiving HBOT experienced improved QOL without consistently significant changes in arm mass, volume or lymphatic drainage. These results call for studies into differential effect in patient sub-groups, and a large-scale, randomized placebo-controlled trial with long-term follow-up to assess the effect of HBOT in patients with soft tissue radiation injuries after breast cancer seems warranted. TRIAL REGISTRATION: Danish Health and Medicines Authority, EUDRACT no. 2015-000,604-25 Ethical committee of the Capitol Region, No. R96-A6604-14-S22.

Preoperative imaging in primary hyperparathyroidism: Are 11 C-Choline PET/CT and 99m Tc-MIBI/123 Iodide subtraction SPECT/CT interchangeable or do they supplement each other?

OBJECTIVE: Preoperative location of hyperfunctioning parathyroid glands (HPGs) is vital when planning minimally invasive surgery in patients with primary hyperparathyroidism (PHPT). Dual-isotope subtraction scintigraphy with 99m Tc-MIBI/123 Iodide using SPECT/CT and planar pinhole imaging (Di-SPECT) has shown high sensitivity, but is challenged by high radiation dose, time consumption and cost. 11 C-Choline PET/CT (faster with a lower radiation dose) is non-inferior to Di-SPECT. We aim to clarify to what extent the two are interchangeable and how often there are discrepancies. DESIGN: This is a prospective, GCP-controlled cohort study. PATIENTS AND MEASUREMENTS: One hundred patients diagnosed with PHPT were included and underwent both imaging modalities before parathyroidectomy. Clinical implications of differences between imaging findings and negative imaging results were assessed. Surgical findings confirmed by biochemistry and pathology served as reference standard. RESULTS: Among the 90 patients cured by parathyroidectomy, sensitivity was 82% (95% confidence interval [CI]: 74%-88%) and 87% (95% CI: 79%-92%) for Choline PET and Di-SPECT, respectively, p = .88. In seven cases at least one imaging modality found no HPG. Of these, neither modality found any true HPGs and only two were cured by surgery. When a positive finding in one modality was incorrect, the alternative modality was correct in approximately half of the cases. CONCLUSION: Choline PET and Di-SPECT performed equally well and are both appropriate as first-line imaging modalities for preoperative imaging of PHPT. When the first-line modality fails to locate an HPG, additional preoperative imaging with the alternate modality offers no benefit. However, if parathyroidectomy is unsuccessful, additional imaging with the alternate modality has merit before repeat surgery.

The Nephroprotective Effect of Mannitol in Head and Neck Cancer Patients Receiving Cisplatin Therapy.

INTRODUCTION: Cisplatin is used as treatment for several different malignancies and a well-known complication is irreversible kidney damage. To protect the kidneys, this treatment is often combined with mannitol infusion to promote osmotic diuresis. Earlier studies investigating the nephroprotective effect of mannitol have shown conflicting results. OBJECTIVE: To investigate changes in kidney function in head and neck cancer patients treated with cisplatin with and without additional mannitol infusion. METHODS: A single center, retrospective cohort study of patients with squamous cell carcinoma of the head and neck receiving radiotherapy with cisplatin. Patient data were collected from November 2013 to December 2014. RESULTS: After exclusion, a total of 78 patients were considered evaluable. They were equally distributed between a mannitol and a non-mannitol group and anthropomorphometrically similar. 51Cr-EDTA clearance declined in the mannitol group from 99.7 (19.9) to 96.4 (20.8) mL/min and in the non-mannitol group from 102.2 (17.8) to 92.3 (23.1) mL/min. CONCLUSIONS: There was a significantly smaller decrease in 51Cr-EDTA clearance in the mannitol group indicating a nephroprotective effect of mannitol.

Weekly ascorbic acid infusion in castration-resistant prostate cancer patients: a single-arm phase II trial.

BACKGROUND: Ascorbic acid (AA) has in vivo cytotoxic properties at concentrations that can only be achieved through intravenous (IV) administration in humans. Treatment with intravenous AA is widely and increasingly used in complementary medicine despite a lack of clinical evidence for the efficacy of this treatment. METHODS: This non-comparative, single-center, phase II trial included patients with chemotherapy-naïve, metastatic castration-resistant prostate cancer (mCRPC) from an outpatient clinic to evaluate the efficacy and safety of IV AA therapy. Patients received weekly infusions of AA (week 1, 5 g; week 2, 30 g; and weeks 3-12, 60 g) followed by efficacy evaluation at 12 weeks. The primary endpoint for efficacy was a 50% reduction in the prostate-specific antigen (PSA) level. The secondary endpoints included changes in health-related quality of life (HRQoL), biomarkers of bone metabolism, inflammation and bone scans. Clinicaltrials.gov identifier: NCT01080352. RESULTS: Twenty-three patients were enrolled in this study, and 20 completed the efficacy evaluation at 12 weeks. The mean baseline PSA level was 43 µg/L. No patient achieved a 50% PSA reduction; instead, a median increase in PSA of 17 µg/L was recorded at week 12. Among the secondary endpoints, no signs of disease remission were observed. In total, 53 adverse events (AEs) were recorded. Eleven were graded as "serious". Three AEs were directly related to AA, and all of which were related to fluid load. CONCLUSIONS: Infusion with 60 g of AA did not result in disease remission. This study does not support the use of intravenous AA outside clinical trials.

Comparison of methods for estimating glomerular filtration rate in head and neck cancer patients treated with cisplatin.

Cisplatin is a chemotherapeutic agent widely used in the treatment of various solid tumors. Cisplatin induces nephrotoxicity and may lead to long-term reduction of kidney function. Consequently, determination of glomerular filtration rate (GFR) is used to monitor potential kidney damage. This study aimed to compare two commonly used algorithms for estimating GFR (eGFR) from plasma creatinine (PCr) with 51Cr-EDTA clearance (CrCl) as a reference method. This was a retrospective single center study of 94 head and neck cancer patients treated with cisplatin. CrCl was performed once before, during, and after treatment, and PCr was measured concurrently. eGFR was assessed from PCr applying the Cockcroft-Gault (CG) and the Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI) equations. Agreement was assessed applying the statistical methods of Bland and Altman. A predefined limit of clinically acceptable variation between CrCl and eGFR of 14% was applied. Comparison of CrCl and eGFRCKD revealed a positive slope of the linear regression line, suggesting proportional bias (p < 0.001). No systematic bias was found for eGFRCG. Pre-treatment, 42 (46%), 53 (56%) and 48 (53%) observations were within the clinically acceptable limit of variation for standardized eGFRCKD, BSA corrected eGFRCKD, and eGFRCG, respectively. The observed body weight changes were significant. In conclusion, estimated GFRCKD cannot sufficiently replace CrCl in the assessment of GFR during treatment with cisplatin due to systematic bias. Consequently, if CrCl is unavailable, then the CG equation is the better choice provided proper attention is paid to the large variation between methods.

A randomised, controlled clinical study on total hip arthroplasty using 4 different bearings: results after 10 years.

PURPOSE: To compare 4 different bearings in total hip arthroplasty (THA) in a randomised controlled clinical study on clinical performance. METHODS: 393 patients with osteoarthritis of the hip or avascular necrosis were included and allocated to 1 of the head-and-cup couples zirconia-on-polyethylene (group A), metal-on-metal (group B), zirconia-on-polyethylene with the liner moulded into the shell (group C), or alumina-on-alumina (group D). In the individual case the surgeon could choose other implants if indicated. RESULTS: 299 patients were operated with the allocated prosthesis. The estimated cumulated prosthesis survival percentages and 95% confidence interval after 10 years were: group A 84.6 (75.8-93.4); group B 95.0 (89.5-100); group C 93.2 (86.7-99.7); group D 66.1 (54.5-77.7). The patients' physical function was significantly improved and remained equally good in all 4 groups, however slightly declining with ageing. The luxation rate was initially high, and equal between the groups, but was reduced by improving the surgical procedure introducing capsule repair by reinsertion of the short external hip rotators. CONCLUSIONS: The metal-on-metal or zirconia-on-polyethylene prostheses had high 10-year survival percentages. The longevity of these bearing couples by themselves was not related to the combination of materials. The zirconia-on-polyethylene prosthesis with the liner mounted peroperatively possibly exhibited cases of backside wear which the corresponding bearing couple with moulded polyethylene (Asian) did not. The alumina-on-alumina bearing performed poorly - it was redesigned after our study initiation and later withdrawn from the market.

Long-term heart function after adjuvant epirubicin chemotherapy for breast cancer.

BACKGROUND: Newer studies raise concern that adjuvant anthracycline treatment for breast cancer (BC) causes long-term heart damage. We aimed to examine whether heart failure or impairment could be demonstrated several years after low-dose epirubicin-based adjuvant treatment. MATERIAL AND METHODS: The study-population was a historical cohort comprising 980 women who were randomized to receive one of two adjuvant regimens for treatment for BC: 7-9 cycles of cyclophosphamide-epirubicin-5-fluorouracil [CEF (600 + 60 + 600 mg/m(2))] or cyclophosphamide-methotrexate-5- fluorouracil [CMF (600 + 40 + 600 mg/m(2))]. We collected information in national registries of death and diagnoses and a sample of 77 survivors was examined with tissue-Doppler imaging (TDI), echocardiography, radionuclide ventriculography and N-terminal-pro-B-type-natriuretic peptide (NT-proBNP), an established marker for heart failure. RESULTS AND CONCLUSION: Median follow-up was 12 years (39 days-20 years). Fifty-one percent had died. Incidence of CHF was 2.6/1000/year and equal in the treatment groups. In the sample, individuals who had received CEF showed no cardiac impairment when compared to individuals who received CMF. NT-proBNP-levels were within normal limits but higher in the CEF-group than in the CMF-group (confidence limits 105-226%, p = 0.03). Results of our study seem reassuring regarding the long-term risk of cardiotoxicity following low-dose adjuvant epirubicin treatment. However, larger, longitudinal studies are needed to establish the clinical implications.