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.

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.

Incidence of cold-induced peripheral neuropathy and dose modification of adjuvant oxaliplatin-based chemotherapy for patients with colorectal cancer.

BACKGROUND: The CAPOX regimen is used for adjuvant treatment of colorectal cancer. A well-known side effect of oxaliplatin, which often leads to dose modification (DM), is acute neuropathy (AN). AN is provoked by cold, and it could therefore be expected that the degree of AN and thereby DM is more pronounced in the winter period compared to the summer period. METHOD: Patients with colorectal cancer who received adjuvant CAPOX from January 2005 to August 2011 were reviewed. Out of 108 patients who received adjuvant CAPOX, the oxaliplatin dose was reduced in 92 (85%) patients due to AN. Seventeen out of 31 (55%) patients already had a DM of oxaliplatin in the second cycle during the winter period (December to February; mean temperature 0.1-1.8°C), while in the summer period (June to August; mean temperature 15.1-16.3°C), only 4 (13%) patients needed DM (OR = 2.5, p = 0.022). CONCLUSION: In this study, we found that the risk of DM and discontinuation of oxaliplatin is highest in the winter period compared to the other seasons. This study draws attention to the importance of training in the proper handling of the acute neurotoxicity of oxaliplatin.

Bisphosphonate treatment in primary breast cancer: results from a randomised comparison of oral pamidronate versus no pamidronate in patients with primary breast cancer.

PURPOSE AND PATIENTS: During the period from January 1990 to January 1996 a total of 953 patients with lymph node negative primary breast cancer were randomised to oral pamidronate (n=460) 150 mg twice daily for 4 years or no adjuvant pamidronate (n=493) in order to investigate whether oral pamidronate can prevent the occurrence of bone metastases and fractures. The patients received adjuvant chemotherapy, loco-regional radiation therapy, but no endocrine treatment. RESULTS: During the follow-up period the number of patients with pure bone metastases was 35 in the control group and 31 in the pamidronate group. The number of patients with a combination of bone and other distant metastases were 22 in the control group and 20 in the pamidronate group. The hazard rate ratio for recurrence in bone in the pamidronate group compared to the control group was 1.03 (95% confidence interval 0.75-1.40) and p=0.86. No effect was observed on overall survival. In a small subgroup of 27 patients from the study, 12 of whom were treated with pamidronate a significant bone preserving effect was observed on bone mineral density in the lumbar spine, but not in the proximal femur. CONCLUSION: The results from the trial do not support a beneficial effect of oral pamidronate on the occurrence of bone metastases or fractures in patients with primary breast cancer receiving adjuvant chemotherapy.