Underrecognition and Underestimation of Disturbances in Calcium-Phosphate Balance in Kidney Transplant Recipients.

Disturbances in mineral metabolism, namely chronic kidney disease-metabolic bone disease, became more profound with impairment of renal function. The aim of the study was to assess how often calcium, phosphate, alkaline phosphatase, and parathyroid hormone (PTH) were measured in kidney transplant recipients relative to hemodialyzed patients. In addition, prevalence of hypercalcemia defined as calcium concentration over 10.5 mg/dL was assessed. PATIENTS AND METHODS: We studied 200 kidney allograft recipients and 100 hemodialyzed patients. Calcium, phosphate, alkaline phosphatase, 25-hydroxy vitamin D, and PTH were obtained from outpatient charts. RESULTS: All the studied parameters were available in 100% of the hemodialyzed patients. In kidney allograft recipients, calcium and phosphate levels were available in 80%, alkaline phosphatase activity was available in 40%, PTH was available in less than 10%, and vitamin D was available in 1%. Hypercalcemia was present in 10% of hemodialyzed patients and in 5% of kidney allograft recipients. Vitamin D analogue was administered to 98% of hemodialyzed patients, whereas vitamin D was administered to 28% of kidney allograft recipients, particularly those with impaired kidney function. In conclusion, calcium and phosphate are seldom assessed on an outpatient basis in kidney allograft recipients, making the diagnosis and treatment of secondary hyperparathyroidism in this population difficult. Care of kidney transplant recipients could be substantially improved, particularly in regard to chronic kidney disease-metabolic bone disease, when regular check-ups for calcium-phosphate balance are implemented and proper treatment could be introduced to prevent further chronic kidney disease-metabolic bone disease.

The utility of FRAX® in predicting bone fractures in patients with chronic kidney disease on hemodialysis: a two-year prospective multicenter cohort study.

We assessed the FRAX® method in 718 hemodialyzed patients in estimating increased risk of bone major and hip fractures. Over two prospective years, statistical analysis showed that FRAX® enables a better assessment of bone major fracture risk in these patients than any of its components and other risk factors considered in the analysis. INTRODUCTION: Despite the generally increased risk of bone fractures among patients with end-stage renal disease, no prediction models for identifying individuals at particular risk have been developed to date. The goal of this prospective, multicenter observational study was to assess the usefulness of the FRAX® method in comparison to all its elements considered separately, selected factors associated with renal disease and the history of falls, in estimating increased risk of low-energy major bone and hip fractures in patients undergoing chronic hemodialysis. METHODS: The study included a total of 1068 hemodialysis patients, who were followed for 2 years, and finally, 718 of them were analyzed. The risk analysis included the Polish version of the FRAX® calculator (without bone mineral density), dialysis vintage, mineral metabolism disorders (serum calcium, phosphate, and parathyroid hormone), and the number of falls during the last year before the study. RESULTS: Over 2 years, low-energy 30 major bone fractures were diagnosed and 13 of hip fractures among them. Area under the curve for FRAX® was 0.76 (95% CI 0.69-0.84) for major fractures and 0.70 (95% CI 0.563-0.832) for hip fractures. The AUC for major bone fractures was significantly higher than for all elements of the FRAX® calculator. In logistic regression analysis FRAX® was the strongest independent risk factor of assessment of the major bone fracture risk. CONCLUSIONS: FRAX® enables a better assessment of major bone fracture risk in ESRD patients undergoing hemodialysis than any of its components and other risk factors considered in the analysis.

Is hemojuvelin a possible new player in iron metabolism in hemodialysis patients?

INTRODUCTION: Hemojuvelin (HJV) is highly expressed in the liver, skeletal muscles, and heart, seems to play a role in iron absorption and release from cells, and has anti-inflammatory properties. Moreover, HJV plays an essential role in the regulation of hepcidin expression, specifically in the iron-sensing pathway. Hepcidin has emerged as a key regulator of iron homeostasis. In this study we tested for the first time the hypothesis that HJV is related to iron metabolism in hemodialysis (HD) patients. METHODS: Iron status, complete blood count, and serum creatinine, albumin, and lipids were assessed, using standard laboratory methods. Serum levels of soluble transferrin receptor (sTFR), high-sensitivity CRP, IL-6, hepcidin, and HJV were measured using commercially available kits. RESULTS: Serum HJV, hepcidin, ferritin, IL-6, hsCRP, and serum creatinine were significantly higher (all P<0.001), whereas serum iron, sTFR, transferrin, hemoglobin, and erythrocyte count were significantly lower in HD patients, compared to healthy volunteers (all P<0.001). In univariate analysis, HJV was strongly correlated (P<0.001) with ferritin, transferrin saturation, and TIBC, as well as with hsCRP, hepcidin, Kt/V (P<0.01) and residual renal function, the presence of diabetes, APKD, and coronary heart disease. Predictors of HJV level in multiple regression analysis were ferritin (beta value was 0.50, P=0.00004) and transferrin saturation (beta value was 0.47, P=0.0002), explaining 81% of the HJV variations. CONCLUSIONS: Serum HJV is elevated in HD patients and related predominantly to kidney function and iron metabolism. However, HJV is probably not correlated to inflammation. HJV appears to be a new player in iron metabolism in these patients.

'2+1' Tricarbonyltechnetium(I) and -rhenium(I) mixed-ligand complexes with N-methylpyridine-2-carboxyamide and isocyanide or imidazole ligands-potential precursors of radiopharmaceuticals.

Complexes of tricarbonyltechnetium(I)-99m and rhenium(I)-188, of '2+1' type: with N-methylpyridine-2-carboxyamide as a neutral bidentate ligand and either tert-butyl 3-isocyanopropionate or imidazole as a monodentate ligand, have been obtained on n.c.a. level. The complexes exhibit moderate lipophilicity and rather high stability in neutral aqueous solutions. The latter has been evidenced from the tests on histidine/cysteine challenge and on protein binding in rat serum. The rhenium complexes studied are much more stable than their technetium analogues. The isocyanopropionate complex may be considered promising model for radiopharmaceutical precursors.

Adipokines, linking adipocytes and vascular function in hemodialyzed patients, may also be possibly related to CD146, a novel adhesion molecule.

Possible correlations between adiponectin, leptin, CD146, a novel adhesion molecule localized at the endothelial junction, and other markers of endothelial cell injury, von Willebrand factor, thrombomodulin, vascular cell adhesion molecule, and intracellular adhesion molecule, and markers of inflammation, tumor necrosis factor-alpha, interleukin-6, and high-sensitivity C-reactive protein in nondiabetic hemodialyzed patients with and without coronary artery disease were studied. Markers of endothelial dysfunction were elevated in hemodialyzed patients, predominantly with coronary artery disease. In multivariate analysis, kinetic urea modeling and plasminogen activator inhibitor-1 remained the only positive predictors of adiponectin. In multivariate analysis, predictors of leptin were triglycerides, tissue plasminogen activator, CD146, and coronary artery disease. In multivariate analysis, predictors of CD146 were age, hemoglobin, and adiponectin. Elevated adiponectin correlated to CD146 may be the expression of a counterregulatory response aimed at mitigating the consequences in endothelial damage and increased cardiovascular risk in renal failure. The data provide further support for a link between adipocytokines, endothelial dysfunction, cardiovascular risk, and renal failure.

Complications following definitive irradiation for cancers of the oral cavity and the oropharynx (in a series of 1134 patients).

PURPOSE: To study the rate and severity of complications in a series of 1134 patients treated by definitive irradiation for tumors of the oral cavity (772 cases) or the oropharynx (361 cases). METHODS AND MATERIALS: Patients were staged as 29.5% T1, 42% T2, 26% T3, 2.5% T4-Tx, and 74.5% N0 tumors. We treated 364 patients with brachytherapy only (192Ir) for the primary lesion. External irradiation and brachytherapy were combined for 770 patients. RESULTS: The results included local control and survival. Out of 1134 patients, 330 had 376 complications. Grade 1 complications occurred in 20% of the patients, Grade 2 in 9%; Grade 3 in 4%; and Grade 4 in 0.2%. Of the Grade 1 complications, 78% were soft tissue and only 24% were bone complications. For the more severe grades (2, 3, and 4), there were 56 soft tissue complications and 90 bone complications out of 1340 patients. The statistical analysis included tumor-related factors and treatment-related factors. For the first two factors, only tumor location was significant. The treatment-related factors significant for complications were studied in univariate and multivariate study. This multivariate study confirmed that for soft tissue complications dose rate and volume treated were important (p < 0.001). It also confirmed that for bone complications, total dose > 80 Gy, dose rate > 0.7 Gy/h, and the absence of leaded protection of the mandible were all important factors. CONCLUSION: This statistical study should allow future reduction of severe complications (Grades 2, 3, 4), if treatment factors inducing them can be taken into account. This is not always possible for very large tumors.

[Value of the combination of external radiotherapy and curietherapy in carcinoma of the velo-tonsillar region. Statistical study of a series of 361 patients]. / Intérêt de l'association radiothérapie externe-curiethérapie dans les carcinomes de la région véloamygdalienne. Etude statistique d'une série de 361 patients.

From 1977 to 1991, we treated 361 carcinomas of the velotonsillar region, either by brachytherapy alone (18 cases), or by an association of external radiotherapy and brachytherapy (343 patients). The latter was performed using a special technique with iridium wires in plastic tubes with afterloading. The primary was the tonsil in 128 patients, the soft palate in 134 patients. We numbered also 9 posterior pillars, 63 anterior pillars and 27 velotonsillar sulcus. According to the UICC staging system (28), we classified the patients in 90 T1, 141 T2, 119 T3, 2 T4, 9 Tx with 230 N0, 93 N1, 9 N2, 20 N3 and 9 Nx. The results at 5 and 10 years show respectively: local control (LC) 80% and 75%, locoregional control 75% and 70%, global survival 53% and 28%, specific survival 63% and 52%. The univariate study shows at 5 years a better local control for T1-T2 (87%) than for T3 (67%) with p = 0.00004. The locoregional control is better for N0 (80%) than for N+ (66%) with p = 0.002, this is the same for global survival (59% versus 42%, p = 0.002). The two groups were individualised according to the primary. Inside each of these groups, the prognosis is identical for different localisations, which allows to put them together. We can therefore distinguish a group A which includes the tonsil, the soft palate and posterior pillar. This group has a better prognosis (controls and survivals) than group B (anterior pillar and velotonsillar sulcus) (p < 0.002). The tumours extended to the mobile tongue, the base of the tongue or the velotonsillar sulcus have a poorer prognosis than those without propagation or with an upwards propagation (p < 0.002). The statistical study of radiobiological factors that can influence the tissular repair shows that there are less recurrences if the duration of treatment is inferior to 55 days and if the interval between external irradiation and brachytherapy is inferior to 20 days. A sufficient safety margin seems also necessary for a good local control. The dose rate within the limits used does not seem to influence the local control and the total dose delivered to the tumour, but this is not surprising since the highest doses are given to the tumours with the smallest regression during external irradiation. The multivariate study for local control shows that the most significant factors are the T, the tumoral localisation and the total duration of treatment. For complications (classified in 4 stages), the dose rate is the most significant factor.

Epidermoid carcinomas of the floor of mouth treated by exclusive irradiation: statistical study of a series of 207 cases.

PURPOSE: Our aim was to study the results and the complications of this series of 207 patients treated from 1976 to 1992 and to compare them with the results of the literature. MATERIAL AND METHODS: The treatment consisted of a combination of external beam irradiation (EBI) (to the tumor and the node areas) and complementary brachytherapy to the primary tumor in 105 cases. In 102 cases, brachytherapy only was delivered to the tumor with or without neck dissection of the node areas. The brachytherapy was performed mostly with the hairpin technique in the beginning (in 61 cases) and subsequently the plastic tube technique with iridium wires. The dosimetry followed the Paris system rules. There were 41% T1, 48% T2, 8% T3, 2% T4 and 1% Tx with 83% N0, 12% N1, 3% N2, 2% N3. Ninety-one percent of patients were male and 9% were female. RESULTS: The local control at 5 years is 97, 72 and 51%, respectively, for T1, T2, T3. The specific survival (without the patients dead of intercurrent disease or second cancer) was 88, 47 and 36%, and the overall survival at 5 years was 71, 42 and 35%. Of note, approximately one third of patients died of intercurrent disease or second cancers (70 patients = 34%). Significant factors that can influence the results are: for local control, the size of the lesion T1/T2/T3 (p < 0.0001); for the locoregional control, the absence of node involvement. The following factors are not significant: age and sex (age significant for survival). The significant treatment factors are the safety margin (p < 0.0003), brachytherapy only on T for T2N0 (p = 0.01). A total duration of treatment of less than 50 days is also significant. The spacing and the total dose (higher dose for large tumors) were not found to be significant. The complications were classified into four grades: grade 1, 17% (median healing, 2 months for soft tissue complications and 5 months for bone complications); grade 2, 12%; grade 3, 6% (frequently requiring surgical resection); grade 4, 0.5% (death, one case). In this series, for the complications, the dose rate, the spacing and the total dose were found not to be significant. CONCLUSION: Carcinomas of the floor of mouth treated by exclusive irradiation have a rather good prognosis and the number of grade 2 and 3 complications remains acceptable. Exclusive brachytherapy is preferable to the combination of EBI plus brachytherapy for T1T2N0.

Influence of tumoral, radiobiological, and general factors on local control and survival of a series of 361 tumors of the velotonsillar area treated by exclusive irradiation (external beam irradiation+brachytherapy or brachytherapy alone)

PURPOSE: To evaluate statistically the factors influencing the therapeutic results. METHODS AND MATERIALS: A statistical study was carried out concerning 361 patients treated from 1977 to 1991 for velotonsillar carcinoma. They received either brachytherapy alone (18) or a combination of external beam irradiation and brachytherapy (343 patients) using an afterloading iridium technique in plastic tubes. The distribution of patients according to the localization was: 128 tonsils, 134 soft palates, 9 posterior pillars, 63 anterior pillars, and 27 glossotonsillar sulcus. The patients were staged as follows: 90 T1, 141 T2, 119 T3, 2 T4, 9 Tx with 230 N0, 93 N1, 9 N2, 20 N3, and 9 Nx. RESULTS: The results at 5 and 10 years show: local control 80% and 74%, locoregional control 75% and 70%, overall survival 53% and 27%, specific survival 63% and 52%, respectively. The univariate study shows at 5 years a better local control for T1T2 (87%) compared with T3 (67%) with p = 0.00004. The locoregional control is better for N0 (80%) than for N+ (55%) with p = 0.002. This is the same for the overall survival (59% vs. 42%, p = 0.002). Tumors with an extension to the mobile tongue or the base have a poor prognosis (p < 0.002). The radiobiological factors show less recurrences if the total duration of the treatment is < 55 days, the number of days between External Beam Irradiation and brachytherapy is < 20. The security margin seems important also. CONCLUSIONS: For the combination external irradiation and brachytherapy, the multivariate study for local control shows that ony T, localization, and the total duration of treatment are significant. For complications, classified into four grades, only the dose rate is significant.

The study of tumoral, radiobiological, and general health factors that influence results and complications in a series of 448 oral tongue carcinomas treated exclusively by irradiation.

PURPOSE: Our aim was to study the different factors that influence the results and complications in a series of 448 carcinomas of the oral tongue treated from January 31, 1972 to December 31, 1986, by brachytherapy (Br) +/- neck dissection (181 cases) or combination of external beam irradiation and brachytherapy (EBI + Br) (267 cases). METHODS AND MATERIALS: The patients distribution (TNM classification 1979) was: 125 T1, 186 T2, 128 T3, 9 T4Tx, 78% N0, and 22% N+. We used guide gutter or plastic tubes technique (Paris system dosimetry). Results at 5 and 10 years are: local control 68% and 64%, locoregional control 58% and 53%, specific survival 45% and 39%, and overall survival 44% and 27%. RESULTS: In the univariate analysis for local control (LC) and overall survival (OS), we considered the tumoral factors. At 5 years, the LC for T1, T2, T3 are 93%, 65%, and 49%, and the OS 69%, 41%, and 25%, respectively (p < 0.002). The lesions of the undersurface of the tongue have a better LC (77%) than other localizations (64%) (p = 0.02). For general factors, the index of general health condition, age, and sex were not significant for LC, but proved significant for OS (p = 0.01). Significant radiobiological factors: the safety margin (expressed by the ratio treated surface on tumoral surface > or = 1.2) is significant for LC and OS. This is the same if the interval between EBI and Br is < or = 20 days. Neither the dose rate, the spacing between the sources, the total dose, nor Br dose were significant, but the last two were adapted according to the infiltration. In the univariate study for grade 2 and 3 complications (tissue and bone), the surface treated (> 12 cm2), and the dose rate > 0.7 Gy/h were significant. CONCLUSION: The multivariate study showed that the small size of the lesion is the most important factor for local control, with brachytherapy alone for T1T2N0 and the number of days between EBI and brachytherapy < or = 20 days. For the complications, the most important factors are the total dose > 80 Gy and a treated surface > 12 cm2.

Salvage irradiation by brachytherapy of velotonsillar squamous cell carcinoma in a previously irradiated field: results in 73 cases.

PURPOSE: The salvage brachytherapy performed in patients presenting velotonsillar carcinoma in a previously irradiated field is evaluated in terms of local control, complications and survival. METHODS AND MATERIALS: Between 1976 and 1990, 73 patients presenting with velotonsillar squamous cell carcinoma in a previously irradiated area were treated at Center Alexis Vautrin with brachytherapy along using an 192Ir implant (afterloading technique) with curative intent. According to the UICC 1987 TNM classification, there were 45 T1 N0, 20 T2 N0, one T3 NO, one T3 N2 and six Tx Nx. RESULTS: The 5-year actuarial local control for T1 N0 and T2 N0 are 80% and 67% respectively. The regional relapse rate was 10% in both groups. Grade 2 complications occurred in 13% of patients and these were neither related to the volume treated nor the dose rate. There were no Grade 3 or 4 complications. The 5-year specific survival is 64%, with a plateau after the 5th year, but the 5-year overall survival is only 30%. Fourty-two percent of the patients in this series died from another carcinoma. All but two of these were related to continued alcohol and tobacco intoxication. CONCLUSION: We conclude that brachytherapy alone (60 Gy) is optimal treatment for patients presenting with velontonsillar carcinoma in a previously irradiated field. The greatest challenge is the screening of these patients and the prevention of subsequent head and neck cancers. Recognizing the fact that these patients are at high risk for subsequent malignancies of upper aerodigestive tract, lung and esophagus, close surveillance is necessary for: (a) early diagnosis and prompt treatment; and (b) development of prevention strategies of field cancerization.