Changes in quality of life 6 months after parathyroidectomy for primary hyperparathyroidism.

Objective: The extent of symptoms due to primary hyperparathyroidism (PHPT) depends on the population being studied. PHPT is mainly discovered incidentally through routine laboratory findings. Less is known about patient-experienced improvement following successful parathyroidectomy. The aim of our study was to assess the changes in the quality of life (QoL) after successful surgery using an SF-36 questionnaire. Design: This is a prospective cohort study based on questionnaires. Methods: Forty consecutive patients diagnosed with PHPT were prospectively administered an SF-36 questionnaire before and 6 months after successful parathyroidectomy. A subgroup of 18 patients answered the questionnaire at 1 and 3 months after surgery. Successful surgery was based on biochemistry and pathology reports as confirmed by an endocrinologist. Results of each SF-36 subcategory were compared to the results at baseline in order to detect changes in patient-reported QoL after successful surgery. Results: There were significant improvements in six of eight SF-36 subcategories: vitality (P = 0.0001), physical functioning (P = 0.04), general health perception (P = 0.004), physical role functioning (P = 0.04), social role functioning (P = 0.004), and mental health perception (P = 0.0001). Changes appeared within a month after surgery with no further significant changes at later time points. Conclusions: Parathyroidectomy significantly improves QoL as measured by a decrease in SF-36 scores as early as 1 month after successful parathyroidectomy. The SF-36 QoL questionnaire is suitable for monitoring changes in patient well-being after successful parathyroidectomy.

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.

Autonomic nervous system activity in primary Raynaud's phenomenon: Heart rate variability, plasma catecholamines and [123 I]MIBG heart scintigraphy.

BACKGROUND AND AIM: Primary Raynaud's phenomenon (pRP) is characterized by an exaggerated response to cold, resulting in the whitening typically of the fingers and toes. The patients are generally perceived as healthy individuals with a benign condition. However, the condition has been associated with increased cardiovascular mortality and changes in autonomic nervous system activity. This study aimed to investigate whether pRP is associated with pervasive changes in autonomic nervous activity. The hypothesis was that patients with pRP have increased sympathetic nervous activity. METHODS: The autonomic nervous activity of 22 patients with pRP was investigated by means of heart rate variability (HRV) and the plasma catecholamine response to head-up tilt and compared with 22 age- and gender-matched controls. In addition, the patients were examined with a [123 I]metaiodobenzylguanidine heart scintigraphy and compared with an external control group. RESULTS: The plasma norepinephrine response to head-up tilt was significantly lower in the patient group than in the control group. Similarly, the heart scintigraphy revealed a lower heart-to-mediastinum ratio in the patient group than in the control group. HRV analysis did not reveal significant differences between the groups. CONCLUSION: The findings of the study showed that the autonomic nervous activity of patients with pRP was altered compared with the activity of healthy individuals. This was observed both during rest and after positional stress, but the findings did not uniformly concur with our initial hypothesis.

An Algorithm for Individual Dosage in Cadmium-Zinc-Telluride SPECT-Gated Radionuclide Angiography.

The aim of the present study was to test an individualised dose without compromising the ease of analysing data when performing equilibrium radionuclide angiography (ERNA) using cadmium-zinc-telluride (CZT) SPECT. From March 2018 to January 2019, 1650 patients referred for ERNA received either an individualised dose of 99mTc-labeled human serum albumin (HSA) according to their age, sex, height, and weight (n = 1567), or a standard dose of 550 MBq (n = 83). The target count rate (CRT) was reduced every two months from 2.7 to 1.0 kcps. A final test with a CRT of 1.7 kcps was run for three months to test whether an agreement within 2% points for the determination of LVEF, on the basis of only two analyses, was obtainable in at least 95% of acquisitions. All the included ERNAs were performed on a dedicated cardiac CZT SPECT camera. When using the algorithm for an individualised dose, we found that agreement between the measured and predicted count rate was 80%. With a CRT of 1.7 kcps, the need for more than two analyses to obtain sufficient agreement for LVEF was 4.9%. Furthermore, this resulted in a mean dose reduction from 550 to 258 MBq. Patients' weight, height, sex, and age can, therefore, be used for individualising a tracer dose while reducing the mean dose.

Locating hyperfunctioning parathyroid glands using 11C-Choline PET/CT: an inter- and intra-observer variation study.

BACKGROUND: Use of 11C-Choline PET/CT is gaining ground in detecting hyperfunctioning parathyroid glands in primary hyperparathyroidism. The purpose of this study was to evaluate the robustness of 11C-Choline PET/CT by assessing intra- and inter-observer agreement to determine whether the method was reader sensitive and therefore should only be performed at highly specialised sites with a high number of cases. PET/CT images of 40 patients diagnosed with primary hyperparathyroidism were anonymised and evaluated three times by three readers: an expert reader and two non-experts (non-experts were experienced in PET/CT imaging, but not in 11C-Choline PET/CT in the setting of primary hyperparathyroidism). Number of hyperfunctioning parathyroid glands, location relative to the thyroid gland and confidence of each assessment (low, moderate or high) were noted, and intra- and inter-observer agreement calculated using Fleiss' kappa method. Sensitivities and specificities of the non-experts were calculated using the expert reader as gold standard. RESULTS: Intra-observer agreement was 'good' to 'near perfect' for all readers. Inter-observer agreement was good between non-experts and the expert, with kappa values ≥ 0.74. Sensitivities between non-experts and the expert were high, > 81%, when assessing which side and 75% when assessing thyroid quadrant. All specificities were > 94%. Reader certainties were 'high' in > 80% of cases for the expert and > 70% and > 65%, respectively for the two non-experts. CONCLUSION: 11C-Choline PET/CT is not reader sensitive for the localisation of hyperfunctioning parathyroid glands and may therefore be safely implemented at sites that have a moderate number of cases. Access to a cyclotron laboratory is, however, a necessity for the production of 11C-Choline. The study was conducted in accordance with the Helsinki 2 declaration and The International Council for Harmonisation Guideline for Good Clinical Practice (ICH_GCP) clinical trial, approved by the Research Ethics Committee of the Capital Region of Denmark (Journal-nr.:H-18012490, date of approval: 18 June 2018) and the Danish Medicines Agency (EudraCT no. 2018-000726-63, date of approval: 6 June 2018). The GCP unit in Eastern Denmark has carried out regular monitoring of the trial according to GCP (ID: 2018-1050).

Infrared Thermography as a Method of Verification in Raynaud's Phenomenon.

Raynaud's phenomenon (RP) is characterized by the episodic whitening of the fingers upon exposure to cold. A recently described thermographic algorithm was proposed as a diagnostic replacement of the currently applied finger systolic pressure (FSP) test. The aim of the study was to evaluate the performance of the thermographic algorithm when applied in patients suspected of having RP. Forty-three patients were examined using thermographic imaging after local cooling of the hands in water of 10 °C for 1 min. The thermographic algorithm was applied to predict the probability of RP. The performance of the algorithm was evaluated with different cut-off levels. A new algorithm was proposed based on patients from the target population. The performance of the tested algorithm was noninferior to the FSP test, when a cut-off level of 0.05 was applied, yielding a sensitivity and specificity of 69% and 58%, respectively. The accuracy was 66%. The FSP test had a sensitivity and specificity of 77% and 37%, respectively, and the accuracy was 59%. The thermographic method proved useful for detecting RP and was able to replace the FSP test as a diagnostic test. The alternative algorithm revealed that other thermographic variables were more predictive of the target population, but this should be verified in future patients.

Characteristic Features of Infrared Thermographic Imaging in Primary Raynaud's Phenomenon.

Raynaud's phenomenon (RP) is characterized by the episodic whitening of the fingers upon exposure to cold. Verification of the condition is crucial in vibration-exposed patients. The current verification method is outdated, but thermographic imaging seems promising as a diagnostic replacement. By investigating patients diagnosed with RP, the study aimed at developing a simple thermographic procedure that could be applied to future patients where verification of the diagnosis is needed. Twenty-two patients with primary RP and 58 healthy controls were examined using thermographic imaging after local cooling of the hands for 1 min in water of 10°C. A logistic regression model was fitted with the temperature curve characteristics to convey a predicted probability of having RP. The characteristics time to end temperature and baseline temperature were the most appropriate predictors of RP among those examined (p = 0.004 and p = 0.04, respectively). The area under the curve was 0.91. The cut-off level 0.46 yielded a sensitivity and specificity of 82% and 86%, respectively. The positive and negative predictive values were 69% and 93%, respectively. This newly developed thermographic method was able to distinguish between patients with RP and healthy controls and was easy to operate. Thus, the method showed great promise as a method for verification of RP in future patients. Trial registration: ClinicalTrials.gov NCT03094910.

Randomized Trial of Acute Changes in Plasma Phosphate After Phosphorus-Standardized Meals in Peritoneal Dialysis.

INTRODUCTION: Hyperphosphatemia is associated with increased morbidity and mortality in patients with chronic kidney disease. The aim of this study was to assess whether a meal with high phosphorus content would affect plasma phosphate in the hours that follow among subjects with end-stage kidney disease on peritoneal dialysis. METHODS: This was a single-blinded randomized cross-over trial of 12 subjects on maintenance peritoneal dialysis, in which subjects were randomized to consume a meal with either high or low phosphorus content on 2 separate trial days. On each trial day, plasma phosphate was measured immediately before consumption of the standardized meal and after 1, 2, 3, and 5 hours. RESULTS: The mean fasting plasma phosphate at baseline was 1.69 ± 0.22 mmol/l. Plasma phosphate was similar between the 2 meals at baseline, as well as at 1, 2, 3, and 5 hours after consumption. The largest observed difference in plasma phosphate between the 2 meals was 0.15 mmol/l, which occurred 5 hours after consumption (high-phosphorus meal 1.75 ± 0.32 mmol/l vs. low-phosphorus meal 1.60 ± 0.14 mmol/l (P = 0.06)). Using summary analyses for repeated measures, we observed a significant difference in the plasma phosphate between the 2 meals (P = 0.03). CONCLUSION: Our results show that in subjects with end-stage kidney disease, a meal with high phosphorus content has only a negligible effect on plasma phosphate compared to a meal with low phosphorus content. Thus, large increases in plasma phosphate cannot be accounted for by a high intake of phosphorus in the hours before blood sampling.

11C-Choline PET/CT vs. 99mTc-MIBI/123Iodide Subtraction SPECT/CT for Preoperative Detection of Abnormal Parathyroid Glands in Primary Hyperparathyroidism: A Prospective, Single-Centre Clinical Trial in 60 Patients.

BACKGROUND: In patients with primary hyperparathyroidism (PHPT) locating hyperfunctioning glands (HPGs) is crucial when planning minimally invasive surgery. Dual-isotope subtraction scintigraphy with 99mTc-MIBI/123Iodide using SPECT/CT and planar pinhole imaging (Method A) has previously shown a sensitivity >93%. However, the method is costly and time consuming and entails a high radiation dose. 11C-Choline PET/CT (Method B) is an appealing candidate method unencumbered by these disadvantages. METHODS: Sixty patients with newly diagnosed PHPT participated and were scanned using both methods prior to parathyroidectomy. We investigated whether sensitivities of Method A and Method B are similar in a method-to-method comparison when using surgical findings as the true location. RESULTS: At the patient level, sensitivities were (A) 0.98 (95% CI: 0.90-1.00) and (B) 1.00 (95% CI: 0.93-1.00). At the gland level, sensitivities were (A) 0.88 (95% CI: 0.78-0.94) and (B) 0.87 (95% CI: 0.76-0.92). With a non-inferiority margin of ∆ = -0.1, we found a 1-sided p-value < 0.001. CONCLUSION: Our methods comparison study found that sensitivity of Method B was not inferior to Method A. We suggest that 11C-Choline PET/CT is a clinically relevant first-choice candidate for preoperative imaging of PHPT and that Method B can likely replace Method A in the near future.

Effect of Dosage of 17ß-Estradiol on Uterine Growth in Turner Syndrome-A Randomized Controlled Clinical Pilot Trial.

CONTEXT: Most Turner syndrome (TS) girls need exogenous estrogen treatment to induce puberty and normal uterine growth. After puberty, the optimal estrogen treatment protocol has not been determined. OBJECTIVE: To compare 2 doses of oral 17ß-estradiol on uterine size. DESIGN: A double-blind, 5-year randomized controlled clinical trial. SETTING: Ambulatory care. PARTICIPANTS: Twenty young TS women (19.2 ± 2.5 years, range 16.0-24.9) participated. Sixteen patients completed the study. No patients withdrew due to adverse effects. INTERVENTION: The lower dose (LD) group took 2 mg 17ß-estradiol/d orally and placebo. The higher dose (HD) group took 4 mg 17ß-estradiol/d orally. MAIN OUTCOME MEASURE(S): Uterine volume evaluated by transabdominal ultrasound yearly. RESULTS: Uterine size increased significantly more in the HD group compared with the LD group (P = 0.038), with a gain in uterine volume within the first 3 years of treatment of 19.6 mL (95% confidence interval [CI] = 4.0-19.0) in the HD group compared with 11.5 mL (95% CI = 11.2-27.9) in the LD group. The difference in 3-year gain was 8.1 mL (95% CI = 0.7-15.9). At the last visit, there were no significant differences in uterine volume between the groups. CONCLUSION: HD oral 17ß-estradiol induces a steeper increase in uterine volume within the first years of treatment compared with the LD. However, the uterine growth potential seems to be the same in most young TS women making the duration of treatment equally significant as estrogen dose, although a few TS women did not experience sufficient uterine growth on 2 mg of estradiol. CLINICALTRIALS.GOV: NCT00134745Abbreviations: BMI, body mass index; BSA, body surface area; DHEAS, dihydroepiandrosteronesulfate; HD, higher dose; HRT, hormone replacement therapy; LD, lower dose; TS, Turner syndrome; US, ultrasound.

5-year outcome after complete mesocolic excision for right-sided colon cancer: a population-based cohort study.

BACKGROUND: The benefits of extensive lymph node dissection as performed in complete mesocolic excision are still debated, although recent studies have shown an association with improved long-term outcomes. However, none of these studies had an intention-to-treat design or aimed to show a causal effect; therefore in this study, we aimed to estimate the causal oncological treatment effects of complete mesocolic excision on right-sided colon cancer. METHODS: We did a population-based cohort study involving prospective data collected from four hospitals in Denmark. We compared the oncological outcome data of patients at one centre performing central lymph node dissection and vascular division after almost complete exposure of the proximal part of the superior mesenteric vein (ie, the complete mesocolic excision group) with three other centres performing conventional resections with unstandardised and limited lymph node dissection (ie, non-complete mesocolic excision; control group). We included data for all patients in the Capital Region of Denmark undergoing elective curative-intent right-sided colon resections for stages I-III colon cancer, as categorised by the Union for International Cancer Control (UICC; 5th edition), from June 1, 2008, to Dec 31, 2013. Patients were followed-up for 5·2 years after surgery. The primary outcome was the cumulative incidence of recurrence after 5·2 years of surgery. Inverse probability of treatment weighting and competing risk analyses were used to estimate the possible causal effects of complete mesocolic excision. This study is registered with ClinicalTrials.gov, number NCT03754075. FINDINGS: 1069 patients (813 in the control group and 256 in the complete mesocolic excision group) underwent curative-intent elective surgery for right-sided colon cancer during the study period. None of the patients were lost to follow-up regarding survival or recurrence status, and consequently no patient was censored in the analyses. The 5·2-year cumulative incidence of recurrence was 9·7% (95% CI 6·3-13·1) in the complete mesocolic excision group compared with 17·9% (15·3-20·5) in the control group, and the absolute risk reduction of complete mesocolic excision after 5·2 years was 8·2% (95% CI 4·0-12·4; p=0·00015). In the control group, 145 (18%) of 813 patients were diagnosed with a recurrence and 281 (35%) died during follow-up, whereas in the complete mesocolic excision group 25 (10%) of 256 patients were diagnosed with a recurrence and 75 (29%) died during follow-up. INTERPRETATION: This study shows a causal treatment effect of central mesocolic lymph node excision on risk of recurrence after resection for right-sided colon adenocarcinoma. Complete mesocolic excision has the potential to reduce the risk of recurrence and improve long-term outcome after resection for all UICC stages I-III of right-sided colon adenocarcinomas. FUNDING: The Tvergaard Fund, Helen Rude Fund, Krista and Viggo Petersen Fund, Olga Bryde Nielsen Fund, and Else and Mogens Wedell-Wedellsborg Fund.

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.

Long-term Functional Outcome After Right-Sided Complete Mesocolic Excision Compared With Conventional Colon Cancer Surgery: A Population-Based Questionnaire Study.

BACKGROUND: Complete mesocolic excision improves the long-term outcome of colon cancer but might carry a risk of bowel dysfunction. OBJECTIVE: This study aimed to investigate whether right-sided complete mesocolic excision is associated with an increased risk of long-term bowel dysfunction and reduced quality of life compared with conventional colon cancer resections. DESIGN: Data were extracted from a population-based study comparing complete mesocolic excision and conventional colon cancer resections and from a national questionnaire survey regarding functional outcome. SETTINGS: Elective right-sided colon resections for stage I to III colon adenocarcinoma were performed at 4 university colorectal centers between June 2008 and December 2014. PATIENTS: Seven hundred sixty-two patients were eligible to receive the questionnaire in November 2015. MAIN OUTCOME MEASURES: The primary outcomes measured were the risk of diarrhea (Bristol stool scale score of 6-7), 4 or more bowel movements daily, and the impact of bowel function on quality of life. Secondary outcomes were other bowel symptoms, chronic pain, and quality of life measured by the European Organisation for Research and Treatment of Cancer QLQ-C30. RESULTS: One hundred forty-one (63.8%) and 324 (59.9%) patients undergoing complete mesocolic excision and conventional resections responded after a median of 3.99 (interquartile range, 2.11-5.32) and 4.11 (interquartile range, 3.01-5.53) years (p = 0.04). Complete mesocolic excision was not associated with increased risk of diarrhea (adjusted OR, 1.07; 95% CI, 0.57-1.95; p = 0.84), 4 or more bowel movements daily (adjusted OR, 1.16; 95% CI, 0.57-2.24; p = 0.68), or lower quality of life (adjusted OR, 0.84; 95% CI, 0.49-1.40; p = 0.50). Complete mesocolic excision was associated nonsignificantly with nocturnal bowel movements, but not associated with chronic pain or other secondary outcomes. LIMITATIONS: This study was limited by the retrospective design with unknown baseline symptoms. Responding patients were younger but without obvious selection bias. The outcome "diarrhea" seemed somehow sensitive to information bias. CONCLUSION: Right-sided complete mesocolic excision seems associated with neither bowel dysfunction nor impaired quality of life when compared with conventional surgery. See Video Abstract at http://links.lww.com/DCR/A665.

The occurrence of fractures after adjuvant treatment of breast cancer: a DBCG register study.

BACKGROUND: Adjuvant treatment in breast cancer patients especially with aromatase inhibitors (AIs) has adverse effects on bone metabolism resulting in an increased occurrence of fractures. In order to demonstrate this occurrence, long-term follow-up studies are necessary. From several national registries in Denmark, it is possible to link data from different sources and analyze this issue. METHODS: A study cohort of 68,842 breast cancer patients prospectively diagnosed and registered in the Danish Breast Cancer Cooperative Group's database during the period 1995-2012 formed the basis of the analysis. These data were matched with data on all types of fractures from the Danish National Patient Register and vital data from the Danish Civil Registration System. RESULTS: After data cleaning 66,502 patients were available for analysis and 16,360 of these had incurred 20,341 fractures with 13,182 patients having just one fracture. These fractures were distributed over 214 specific fracture sites. An extended multivariable Cox regression model revealed significant association between the occurrence of fractures and age, menopause, Charlson comorbidity index (CCI) and endocrine therapy such that late menopause and tamoxifen treatment were associated with a lower occurrence and AI treatment, age and CCI were associated with a higher occurrence of fractures. CONCLUSION: Before advising adjuvant therapy with AIs fragile patients with chronic diseases should receive special attention in order to reduce the incidence of fractures in this vulnerable group of patients.

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.

Dosage of estradiol, bone and body composition in Turner syndrome: a 5-year randomized controlled clinical trial.

OBJECTIVE: Reduced bone mineral density (BMD) is seen in Turner syndrome (TS) with an increased risk of fractures, and body composition is characterized by increased body fat and decreased lean body mass. To evaluate the effect of two different doses of oral 17B-estradiol in young TS women on bone mineral density (BMD), biochemical markers of bone turnover and body composition with the hypothesis of a positive effect of the higher dose. DESIGN: A double-blind 5-year randomized controlled clinical trial. 20 young TS women participated. Inclusion criteria were diagnosis of TS, age 15-25 years and current treatment with 2 mg oral estradiol daily. METHODS: The low-dose (LD) group was administered 2 mg 17B-estradiol/day orally and placebo, the high-dose (HD) group was administered 2 + 2 mg 17B-estradiol/day orally. Main outcome measures were whole body and regional bone mineral density (BMD), lean body mass (LBM), fat mass (FM) measured yearly by DXA scan and resorptive and formative bone markers in serum. RESULTS: BMD, whole body and regional, increased over time with an attenuation toward the end of the study, and bone turnover markers decreased over time, both with no differences between the treatment groups (P = 0.2-0.9). LBM increased significantly more in the HD group (P = 0.02). FM remained stable in both groups. CONCLUSIONS: A steady increase in BMD over time in TS was found similar to healthy young women. The higher estrogen dose did not differentially affect BMD or bone markers. The positive effect on body composition may have long-ranging health benefits in TS.

The pathological phenotype of colon cancer with microsatellite instability.

INTRODUCTION: Colorectal cancer is a common malignant disease, caused by different aetiologies and molecular pathways. Heterogeneous results have been published regarding the association of microsatellite instability and clinicopathological features. The aim of this study was to compare clinicopathological features of microsatellite unstable tumours with stable ones. METHODS: Data were collected retrospectively, but the pathological analyses were all made prospectively. The study included a total of 833 patients undergoing resection of their colon tumour at Nordsjællands Hospital - Hillerød, with mismatch repair analysis from 1 January 2007 to 30 November 2012. The study was performed in a setting with complete mesocolic excision surgery and post-operative expert pathological examination of the tumours. Mismatch repair analysis was done by immuno-histochemical staining for the mismatch repair proteins: pMLH1, pMSH2, pMSH6 and pPMS2 for the determination of microsatellite instability. Microsatellite instability was defined as deficient expression of one or more of these proteins. RESULTS: Of the 833 patients, 177 had microsatellite instable tumours (21%). Using multivariable logistic regression analysis, we demonstrated that microsatellite unstable cancers were significantly associated with a lower degree of lymph node metastases (odds ratio (OR) = 0.92), distant metastases (OR = 0.33) and tumour budding (OR = 0.41). CONCLUSIONS: We found that microsatellite unstable tumours show a pathological profile that appears less aggressive than the pathological profile of stable tumours. FUNDING: none. TRIAL REGISTRATION: not relevant.

Impact of extracorporeal blood flow rate on blood pressure, pulse rate and cardiac output during haemodialysis.

BACKGROUND: If blood pressure (BP) falls during haemodialysis (HD) [intradialytic hypotension (IDH)] a common clinical practice is to reduce the extracorporeal blood flow rate (EBFR). Consequently the efficacy of the HD (Kt/V) is reduced. However, only very limited knowledge on the effect of reducing EBFR on BP exists and data are conflicting. The aim of this study was to evaluate the effect and the potential mechanism(s) involved by investigating the impact of changes in EBFR on BP, pulse rate (PR) and cardiac output (CO) in HD patients with arteriovenous-fistulas (AV-fistulas). METHODS: We performed a randomized, crossover trial in 22 haemodynamically stable HD patients with AV-fistula. After a conventional HD session each patient was examined during EBFR of 200, 300 and 400 mL/min in random order. After 15 min when steady state was achieved CO, BP and PR were measured at each EFBR, respectively. RESULTS: Mean (SD) age was 71 (11) years. Systolic BP was significantly higher at an EBFR of 200 mL/min as compared with 300 mL/min [133 (23) versus 128 (24) mmHg; P < 0.05], but not as compared with 400 mL/min [133 (23) versus 130 (19) mmHg; P = 0.20]. At EBFR of 200, 300 and 400 mL/min diastolic BP, mean arterial pressure, PR and CO remained unchanged. CONCLUSION: Our study does not show any consistent trend in BP changes by a reduction in EBFR. Reduction in EBFR if BP falls during IDH is thus not supported. However, none of the patients experienced IDH. Further studies are required to evaluate the impact of changes in EBFR on BP during IDH.