Reelevation of parathyroid hormone level after parathyroidectomy in patients with primary hyperparathyroidism: importance of decreased renal parathyroid hormone sensitivity

BACKGROUND: We hypothesized that impaired peripheral sensitivity to parathyroid hormone (PTH) may play a role in reelevation of PTH after successful operation for primary hyperparathyroidism (pHPT). METHODS: Factors affecting reelevation of PTH were determined in 90 patients who underwent parathyroidectomy for pHPT. PTH/nephrogenous cyclic adenosine monophosphate ratio, as an index of renal resistance to PTH, was examined in relation to factors shown to influence reelevation of PTH. RESULTS: Serum PTH levels were elevated above the upper limit of normal in 23 patients (26%) at 1 week and in 39 patients (43%) at 1 month after parathyroidectomy. These 39 normocalcemic patients with elevated serum PTH at 1 month after parathyroidectomy had a higher preoperative serum level of PTH and lower serum phosphate and 25-hydroxyvitamin D (25OHD) concentrations than those with normal PTH (n = 59). Elevated PTH and low 25OHD were shown by multivariate analysis to be significant predictors of reelevation of PTH. Renal resistance to PTH was higher in patients with vitamin D deficiency or renal insufficiency than in patients with normal serum vitamin D concentrations or normal renal function, and it increased according to increases in levels of PTH. CONCLUSIONS: The mechanism of PTH reelevation in patients with pHPT after successful parathyroidectomy appears to be renal resistance to PTH.     

Intrajoint comparisons of gene expression patterns in human osteoarthritis suggest a change in chondrocyte phenotype.

Osteoarthritis (OA) is a degenerative cartilage disease with varying degrees of severity within a given joint. The purpose of this study was to define a sampling procedure for comparing human minimal and advanced OA cartilage in the same patient and to determine basic patterns of gene expression in these regions. A specific hypothesis under study was that the expression level of Bcl-2 would correlate with Sox9 and aggrecan mRNA expression in vivo as has been demonstrated in vitro. Femoral condylar advanced OA cartilage was located within 1cm of overt lesions, and minimal cartilage was taken from areas with no obvious surface defects. Histological sections were scored for disease severity and chondroitin sulfate and hydroxyproline content was determined. The expression level of nine specific genes (aggrecan, collagen type II, Bcl-2, Sox9, Link protein, osteopontin, and MMP-13, -3, and -9) was determined by quantitative real time PCR. The scores for fibrillation, chondrocyte cloning, and proteoglycan depletion were significantly different between advanced and minimal OA cartilage. The advanced OA cartilage had significantly less chondroitin sulfate than the minimal OA cartilage. Osteopontin mRNA expression showed a 3.6-fold increase in advanced compared to minimal OA cartilage. In contrast, the level of mRNA coding for aggrecan, link protein, Bcl-2, Sox9 and MMP-3, -9, -13 were all decreased in advanced compared to minimal cartilage in the majority of the patients studied. Collagen type II mRNA expression displayed a wide-range of variation. A statistically significant correlation was observed both between Bcl-2 and Sox9 mRNA level, and between Bcl-2 and aggrecan mRNA expression. The patient matched comparison of minimal and advanced OA cartilage revealed differences in cellular and tissue characteristics, and changes in gene expression that may be involved in OA progression. In addition, Bcl-2 may also play a role in regulating the expression of aggrecan through Sox9 in vivo as well as in vitro.     

Xanthogranulomatous cholecystitis: the use of preoperative CT findings to differentiate it from gallbladder carcinoma

Background and aim  A retrospective analysis was performed on 32 patients with histologically confirmed xanthogranulomatous cholecystitis (XGC) and 21 patients with gallbladder carcinoma who underwent surgical treatment between 1998 and 2007. Methods  All patients underwent preoperative CT scanning. The CT features analyzed were: the presence of intramural hypoattenuated nodules or bands, mucosal line, the patterns of wall thickening and enhancement, and the presence of stones in the gallbladder. The variables of the CT findings with XGC were analyzed using multivariate logistic regression analysis. Results  Intramural hypoattenuated nodules were observed in 21 patients (65%) with XGC, but in only six patients (29%) with gallbladder carcinoma (P < 0.01). The mucosal line was observed in 27 patients (84%) with XGC and in only four patients (19%) with gallbladder carcinoma (P < 0.0001). Gallstones were noted in 24 patients (75%) with XGC and five patients (24%) with gallbladder carcinoma (P < 0.001). There was no significant difference in the pattern of gallbladder wall thickening (diffuse or focal) and the presence of changes outside the gallbladder. Multivariate logistic regression analysis revealed from the CT features that the enhanced continuous mucosal line (P = 0.0013) and the presence of gallstones (P = 0.0072) were independently correlated with XGC. Conclusion  CT features of the enhanced continuous mucosal line in a thickened gallbladder wall, together with gallstones in a patient with chronic gallbladder disease, are highly suggestive of XGC. Accurate diagnosis of XGC may therefore indicate the need to select a less aggressive surgical approach.     

Successful treatment for lung cancer associated with pulmonary sequestration

We encountered a 69-year-old man with lung adenocarcinoma and pulmonary sequestration. The cancer lesion was located in the left upper lobe, with sequestration of the left lower lobe. Left upper lobectomy was performed after induction chemoradiotherapy, but the sequestered lung lobe was preserved because the preoperative respiratory function was poor. Preservation of the sequestered lung during surgery for lung cancer should be considered in patients who have poor respiratory function and no signs of respiratory infection.     

Half clamping of the infrahepatic inferior vena cava reduces bleeding during a hepatectomy by decreasing the central venous pressure

Background and aims  Bleeding from the hepatic vein is closely related to central venous pressure (CVP). To evaluate the effect of low central venous pressure during a hepatectomy, the infrahepatic inferior vena cava (IVC) was half clamped. Patients and methods  Between 2006 and 2007, 20 patients undergoing major hepatectomy with the IVC half clamping (half-clamping group) were compared with 58 patients undergoing hepatectomy without IVC half clamping between 2003 and 2005 (control group). The types of liver resection, amount of blood loss during the hepatectomy, volume of blood transfusion, length of hospital stay, and complications were compared between the two groups. Results  In the half-clamping group, blood loss was decreased in comparison to the control group (p = 0.041) and the suprahepatic CVP was low (2.4 ± 1.8 mmHg; p = 0.0002). The diameter at the root of the right hepatic vein was reduced in comparison to before clamping (5.8 ± 1.6 mm; p < 0.001). There were no complications of half clamping on any hemodynamic and blood electrolytic parameters. Conclusion  Using the half clamping technique of the IVC, intra-operative CVP was maintained below 3 mmHg without any side effects, and the low CVP significantly reduced the bleeding from hepatic veins during a major hepatectomy.     

Differentiation of tumor recurrence from radiation-induced pulmonary fibrosis after stereotactic ablative radiotherapy for lung cancer: characterization of 18F-FDG PET/CT findings

Objective

Stereotactic ablative radiotherapy (SABR), also known as stereotactic body radiotherapy (SBRT), is now a standard treatment option for patients with stage I non-small cell lung cancer or oligometastatic lung tumor who are medically inoperable or medically operable but refuse surgery. When mass-like consolidation is observed on follow-up CT after SABR, it is sometimes difficult to differentiate tumor recurrence from SABR-induced pulmonary fibrosis. In this study, we evaluated the role of ¹⁸F-fluorodeoxyglucose positron emission tomography combined with computed tomography (FDG-PET/CT) in differentiating tumor recurrence from radiation fibrosis after SABR.

Methods

Between June 2006 and June 2009, 130 patients received SABR for stage I non-small cell lung cancer or metastatic lung cancer at our institution. Fifty-nine patients of them were imaged with FDG-PET/CT after SABR. There were a total of 137 FDG-PET/CT scans for retrospective analysis. The FDG uptake in the pulmonary region was assessed qualitatively using a 3-point scale (0, none or faint; 1, mild; or 2, moderate to intense), and the shape (mass-like or non mass-like) was evaluated. For semi-quantitative analysis, the maximum standardized uptake value (SUV_max) was calculated.

Results

Sixteen of 59 patients had local failure. In recurrent tumor, the combination of intensity grade 2 and mass-like shape was most common (21/23; 91 %). By contrast, in cases of radiation fibrosis, the combination of intensity grade 0 or 1 and non mass-like shape was most common (48/59; 81 %). The SUV_max of tumor recurrence after 12 months was significantly higher than that of radiation fibrosis (8.0 ± 3.2 vs. 2.1 ± 0.9, p < 0.001), and all tumor recurrence showed the SUV_max > 4.5 at diagnosis of local failure. At ≥12 months after SABR, these two variables, the combination of intensity 2 and mass-like FDG uptake or SUV_max > 4.5 acquired a significant high predictive value of local recurrence, finding sensitivity 100 % and specificity 100 % for both of them.

Conclusions

The combination of FDG uptake patterns and SUV_max was useful for distinguishing tumor recurrence from radiation fibrosis after SABR.     

Associations among q-space MRI, diffusion-weighted MRI and histopathological parameters in meningiomas

Objectives

The purposes of this MR-based study were to calculate q-space imaging (QSI)–derived mean displacement (MDP) in meningiomas, to evaluate the correlation of MDP values with apparent diffusion coefficient (ADC) and to investigate the relationships among these diffusion parameters, tumour cell count (TCC) and MIB-1 labelling index (LI).

Methods

MRI, including QSI and conventional diffusion-weighted imaging (DWI), was performed in 44 meningioma patients (52 lesions). ADC and MDP maps were acquired from post-processing of the data. Quantitative analyses of these maps were performed by applying regions of interest. Pearson correlation coefficients were calculated for ADC and MDP in all lesions and for ADC and TCC, MDP and TCC, ADC and MIB-1 LI, and MDP and MIB-1 LI in 17 patients who underwent subsequent surgery.

Results

ADC and MDP values were found to have a strong correlation: r?=?0.78 (P?=?<0.0001). Both ADC and MDP values had a significant negative association with TCC: r?=?–0.53 (p?=?0.02) and –0.48 (P?=?0.04), respectively. MIB-1 LI was not, however, found to have a significant association with these diffusion parameters.

Conclusion

In meningiomas, both ADC and MDP may be representative of cell density.

Key Points

? Diffusion-weighted MRI offers possibilities to assess the aggressiveness of meningiomas. ? The q-space imaging-derived mean displacement correlates strongly with apparent diffusion coefficients. ? Both diffusion parameters showed a strong negative association with tumour cell counts. ? Derived mean displacement may help assess the aggressiveness of meningiomas preoperatively.     

Thallium-201 myocardial SPECT findings at rest in sarcoidosis

In 41 patients with sarcoidosis (diagnosed according to criteria recommended by the Committee on Diffuse Pulmonary Disease, Ministry of Health and Welfare, Japan 1988), thallium-201 (²⁰¹Tl) myocardial SPECT was performed to investigate: (1) the ability of²⁰¹Tl SPECT to detect cardiac involvement of sarcoidosis with images recorded at rest and 2 hours later, and (2) the relationships between²⁰¹Tl myocardial SPECT findings and the activity of sarcoidosis or endomyocardial biopsy findings. As to the abnormal findings in²⁰¹Tl myocardial SPECT, (1) a low density area was seen in 13 of 41 cases (31.7%) and non-uniform uptake was found in 17 cases (41.5%), (2) the mean washout ratio (n=39) was 16.5±7.4%, which is significantly (p < 0.05) lower than that found in normal subjects, 23.9±7.5 % (n=10). Of the 19 patients judged visually to be normal, 5 patients had a reduced mean washout ratio less than 12%. Thus, the incidence of abnormal findings including all types of abnormality, on²⁰¹Tl myocardial SPECT in sarcoidosis was 63.4% (26/41 cases). In studying the relationship between²⁰¹Tl myocardial SPECT findings and the activity of sarcoidosis (as measured by the serum ACE (angiotensin converting enzyme) or lysozyme level, or the presence of more than 30% symphocyte fraction in BALF (broncho-alveolar lavage fluid)), 20 (80%) of 25 cases with²⁰¹Tl abnormality were judged to be active sarcoidosis, while only 6 (37.5%) of 16 cases with normal findings on²⁰¹Tl SPECT were judged to be active. This suggests that there is a significant (p < 0.01) relationship between the presence or absence of an abnormal finding on²⁰¹Tl myocardial SPECT and the activity of sarcoidosis. Among 13 patients examined by endomyocardial biopsy, 10 patients had abnormal findings on²⁰¹Tl myocardial SPECT and 7 of these 10 patients had no histological evidence of cardiac sarcoidosis. In all of these 7 patients, however, sarcoidosis was judged to be active. This suggest that endomyocardial biopsy is of limited value in the diagnosis of cardiac sarcoidosis.     

Dietary calcium and phosphorus ratio regulates bone mineralization and turnover in vitamin D receptor knockout mice by affecting intestinal calcium and phosphorus absorption.

The effects of the dietary Ca and P ratio, independent of any vitamin D effects, on bone mineralization and turnover was examined in 60 VDRKO mice fed different Ca/P ratio diets. High dietary Ca/P ratio promoted bone mineralization and turnover with adequate intestinal Ca and P transports in VDRKO mice. INTRODUCTION: To clarify the effects of the dietary calcium (Ca) and phosphorus (P) ratio (Ca/P ratio) on bone mineralization and turnover in null-vitamin D signal condition, vitamin D receptor knockout (VDRKO) mice were given diets containing different Ca/P ratios. MATERIALS AND METHODS: Five groups of 4-week-old VDRKO mice, 10 animals each, were fed diets for 4 weeks. Group 1 was wild-type littermate mice, fed the diet containing 0.5% Ca and P (Ca/P = 1). Group 2 was the control and was fed a similar diet (Ca/P = 1). Groups 3, 4, 5, and 6 were fed the following diets: 0.5% Ca and 1.0% P (Ca/P = 0.5), 1.0% Ca and 1.0% P (Ca/P = 1), 1.0% Ca and 0.5% P (Ca/P = 2), and 0.5% Ca and 0.25% P (Ca/P = 2). RESULTS AND CONCLUSIONS: Compared with group 2, serum calcium and phosphorus levels in groups 4-6 significantly increased. Serum parathyroid hormone levels increased in group 3 and decreased in group 5. The amounts of intestinal calcium absorption decreased in groups 3 and 4. Phosphorus absorption increased in group 3 and decreased in groups 4-6. Bone mineral content (BMC) and bone mineral density (BMD) of the femur in group 3 significantly decreased and increased in group 5. In the primary spongiosa of the proximal tibia, the trabecular bone volume (BV/TV) and osteoid thickness (O.Th) in group 3 significantly increased, and decreased in group 6. In groups 5 and 6, the numbers of the trabecular osteoclasts increased. In groups 2 and 4, and the secondary spongiosa was identified in 5 of 10 mice. In group 3, there was no secondary spongiosa in either mouse. Osteoid maturation time (OMT) significantly decreased, and bone formation rate (BFR/BS) increased in groups 4-6. These data indicate that the dietary Ca/P ratio regulates bone mineralization and turnover by affecting the intestinal calcium and phosphorus transports in VDRKO mice. They may suggest the existence of Ca/P ratio-dependent, vitamin D-independent calcium and phosphorus transport system in the intestine.     

Diagnostic accuracy of the apparent diffusion coefficient in differentiating benign from malignant uterine endometrial cavity lesions: initial results

Our purpose is to evaluate the diagnostic accuracy of apparent diffusion coefficient (ADC) measurement in differentiating malignant from benign uterine endometrial cavity lesions. We retrospectively evaluated 25 uterine endometrial cavity lesions in 25 female patients: endometrial carcinoma (n = 11), carcinosarcoma (n = 2), submucosal leiomyoma (n = 8), and endometrial polyp (n = 4). Diffusion-weighted images were performed at 1.5 T with b factors of 0–1,000/mm². The region of interest was defined within the tumor on T2-weighted EPI image and then manually copied to an ADC map. Thereby, the ADC value was obtained. We compared ADC values between malignant and benign lesions using Student’s t-test. The mean and standard deviation of ADC values (×10⁻³ mm²/s) were as follows: endometrial carcinoma, 0.98±0.21; carcinosarcoma, 0.97±0.02; submucosal leiomyoma, 1.37±0.28; and endometrial polyp, 1.58±0.45. The ADC values differed significantly between malignant (0.98±0.19) and benign lesions (1.44±0.34) (P < 0.01). We defined malignant tumors as cases with an ADC value less than 1.15 × 10⁻³ mm²/s for obtaining the highest accuracy. Sensitivity, specificity, and accuracy were 84.6%, 100%, and 92%, respectively. ADC measurement can provide useful information in differentiating malignant from benign uterine endometrial cavity lesions.