A phase II study of tivozanib in patients with metastatic and nonresectable soft-tissue sarcomas.

Background: Soft tissue sarcomas (STSs) overexpress vascular endothelial growth factors (VEGF) and VEGF-receptors (VEGFR) activation have been associated with tumor aggressiveness. Tivozanib is a potent small molecule tyrosine kinase inhibitor against VEGFR1-3, with activity against PDGFRα/ß and cKIT. The primary endpoint of this study was progression free survival (PFS) rate at 16 weeks. Secondary end points were overall survival (OS), response rate, safety and correlative studies. Patients and methods: A Simon two-stage phase II trial was performed using tivozanib given orally at 1.5 mg daily, 3 week on 1 week off on a 28 day cycle until disease progression or intolerable toxicity. Results: Fifty-eight patients were enrolled and treated with tivozanib. Leiomyosarcoma was the most common STS histological type in our cohort (47%) and 27 patients (46%) had received at least 3 lines of therapy prior to study entry. Up to 24 patients (41%) had prior VEGF targeted therapies. Partial response and stable disease were observed in 2 (3.6%) and 30 (54.5%) patients. The 16 week PFS rate was 36.4% [95% confidence interval (CI) 23.7-49.1] and a median PFS of 3.5 months (95% CI 1.8-3). Median OS observed was 12.2 months (95% CI 8.1-16.8). The most frequent all grade toxicities were fatigue (48.3%), hypertension (43.1%), nausea (31%) and diarrhea (27.6%). The most common grade three toxicity was hypertension (22.4%). Correlative studies demonstrate no correlation between the expression of VEGFR 1, 2 or 3, PDGFRα/ß or FGF, and activity of tivozanib. Conclusion: Tivozanib was well tolerated and showed antitumor activity with a promising median PFS and PFS rate at 4 months in a heavily pretreated population of metastatic STSs. Our results support further studies to assess the clinical efficacy of tivozanib in STS. Clinical Trial Number: NCT01782313.

A combination of ultrasound-guided rectus sheath and transversus abdominis plane blocks is superior to either block alone for pain control after gynecological transumbilical single incision laparoscopic surgery.

PURPOSE: To investigate the efficacy of the combination of ultrasound-guided rectus sheath (RS) and transversus abdominis plane (TAP) blocks compared with TAP or RS block alone in gynecological single-incision laparoscopic surgery (SILS). MATERIALS AND METHODS: Bilateral TAP blocks (Group A, n = 12), TAP and RS blocks (Group B, n = 12), and RS blocks (Group C, n = 12) with 40 ml ropivacaine/patient were performed for ovarian tumor SILS. The analgesic effects were evaluated using a numerical rating scale (NRS) at zero, six, 12, 24, and 48 hours post-surgery. RESULTS: Umbilical pain on completion of general anesthesia was significantly less frequent in Group B (1/12) than Group A (7/12) (p = 0.03). The postoperative NRS scores were significantly lower in Group B than Group A at zero (p = 0.02) and six (p = 0.03) hours and Group C at zero (p = 0.001), six (p = 0.02), and 12 (p = 0.004) hours. CONCLUSION: The combination of RS and TAP blocks reduced early postoperative pain compared with RS or TAP block alone for gynecological SILS.

Increased undercarboxylated osteocalcin/intact osteocalcin ratio in patients undergoing hemodialysis.

UNLABELLED: Serum undercarboxylated osteocalcin (ucOC)/intact osteocalcin (iOC) ratio increased >1.0 in the patients undergoing hemodialysis, particularly in those with high bone turnover state. Consequently, serum ucOC/iOC ratio might lose its significance as a bone metabolic marker to indicate vitamin K deficiency in hemodialysis patients. INTRODUCTION: Serum intact osteocalcin (iOC), undercarboxylated OC (ucOC), and the ucOC/iOC ratio are considered clinically relevant indices in pre-dialysis chronic kidney disease (CKD) and hemodialysis (HD) patients, despite their accumulation in uremic serum. METHODS: Serum iOC and ucOC were measured along with serum intact parathyroid hormone (iPTH), bone alkaline phosphatase (BAP), and tartrate-resistant acid phosphatase (TRACP)-5b in 89 pre-dialysis CKD and 189 HD patients. RESULTS: Serum iOC and ucOC showed significantly negative correlations with estimated glomerular filtration rate in pre-dialysis CKD patients, although serum ucOC/iOC ratio did not correlate. Serum ucOC was significantly greater in HD patients than in pre-dialysis CKD patients, while serum iOC did not differ significantly, resulting in serum ucOC/iOC ratio >1.0 in 135 (71.4%) out of 189 HD patients. HD patients with high serum ucOC/iOC ratio (>1.0) had a significantly younger age and significantly higher values of body mass index, serum creatinine, albumin, phosphate, iPTH, and TRACP-5b than those with low ucOC/iOC ratio (≤ 1.0). The baseline iPTH and P1NP correlated with the changes of the ucOC/iOC ratio during the 2 days of the inter-dialytic period. Multivariate analysis showed that log [ucOC/iOC] in HD patients was significantly associated with log [iPTH], log [BAP], or log [TRACP-5b]. CONCLUSIONS: Serum ucOC/iOC ratio >1.0 was observed in as high as 71.4% of HD patients, preferentially with high bone turnover state, in comparison with pre-dialysis CKD patients. These data suggested that serum ucOC/iOC ratio might lose its significance as a bone metabolic marker to indicate vitamin K deficiency in HD patients.

Effectiveness of ultrasound-guided transversus abdominis plane block and rectus sheath block in pain control and recovery after gynecological transumbilical single-incision laparoscopic surgery.

PURPOSE: To evaluate the effectiveness of ultrasound-guided transversus abdominis plane (TAP) and rectus sheath (RS) blocks in pain management and recovery after gynecological single-incision laparoscopic surgery (SILS). MATERIALS AND METHODS: Abilateral TAP block (Group A, n = 9), bilateral TAP and RS blocks (Group B, n = 10), and a bilateral RS block (Group C, n = 9) with 40 ml ropivacaine per patient were conducted in 28 patients undergoing SILS for ovarian tumors. A pain score and walking distance in a 6-minute walk test (6MWT) were examined. RESULTS: Pain scores were significantly lower on postoperative day (POD) 3 than on POD 1 in Groups B (p = 0.03) and C (p = 0.02). The walking distance on POD 3 was comparable with that before surgery in Group C (p = 0.75), but shorter in Groups A (p = 0.004) and B (p = 0.02). CONCLUSIONS: The RS block alone was the most effective in relieving pain and accelerating general recovery after gynecological SILS.

Increased active PTH(1-84) fraction as a predictor of poor mortality in male hemodialysis patients.

UNLABELLED: We reported previously that serum parathyroid hormone [PTH(1-84)]/intact PTH[PTH(1-84) + PTH(7-84)] ratio provides the better marker for parathyroid function and bone turnover state than serum PTH level itself. The present study demonstrated that higher PTH(1-84)/intact PTH ratio, but not serum PTH(1-84) and intact PTH, predicted higher all-cause mortality in 177 male hemodialysis patients. INTRODUCTION: We reported that PTH(1-84)/intact PTH ratio provides a clinically relevant marker for parathyroid function and the resultant bone turnover state. The purpose of our study was to investigate the association of PTH(1-84)/intact PTH ratio with all-cause mortality (ACM) in male hemodialysis patients. METHODS: The study was performed for 70 months. Serum PTH in 177 male hemodialysis patients was measured with PTH(1-84)-specific whole PTH assay and intact PTH assay which cross-reacts with N-truncated PTH including PTH(7-84). RESULTS: The patients (n = 177) were divided into higher and lower halves based on serum levels of PTH(1-84)/intact PTH ratio (cutoff value, 0.484), intact PTH (143.8 pg/mL), and PTH(1-84) (64.1 pg/mL). In Kaplan-Meier analysis, the higher group in whole PTH/intact PTH ratio had significantly higher ACM than the lower group (P = 0.020 by log-rank test), in contrast with the insignificant difference between the higher and lower groups in intact PTH and PTH(1-84). Multivariate Cox regression hazard analysis identified higher log [PTH(1-84)/intact PTH ratio], but not log intact PTH or log PTH(1-84) as a significant independent predictor [hazard ratio 14.428 (95% CI 2.486-83.728)] for ACM after adjustment for various factors including age, hemodialysis duration, presence/absence of diabetes mellitus, BMI, log C-reactive protein, serum albumin, calcium, and phosphate. The association existed between log [PTH(1-84)/intact PTH ratio] and ACM in those without vitamin D administration (n = 95). CONCLUSION: Higher PTH(1-84)/intact PTH ratio, which provides a relevant marker for parathyroid function, may be a significant predictor of ACM in male hemodialysis patients.

Phase II study of the HSP90-inhibitor BIIB021 in gastrointestinal stromal tumors.

BACKGROUND: HSP90 inhibition leads to proteosomal degradation of activated KIT and has in vitro activity against gastrointestinal stromal tumors (GIST). BIIB021 is an oral non-ansamycin HSP90 inhibitor. We carried out a phase II study of BIIB021 in patients with GIST refractory to imatinib and sunitinib. PATIENTS AND METHODS: The primary end-point was metabolic partial response (mPR) as assessed by fluorodeoxyglucose positron emission tomography (FDG-PET). The secondary end-points were pharmacokinetic assessments of BIIB021 and pharmacodynamic assessments of HSP70. Twenty-three patients were treated on two schedules: 12 pts received 600 mg twice a week (BIW) and 11 patients received 400 mg three times a week (TIW). All had prior imatinib and sunitinib but stopped>14 days before starting BIIB021. RESULTS: The median age was 59 years (33-88 years), 61% male, 44% Eastern Cooperative Oncology Group 1 (ECOG1). The best response was PR by FDG-PET for five patients (3/12 at 600 mg BIW and 2/9 at 400 TIW) for an overall response rate of 22%. The response duration was 25-138 days. Adverse events (AEs) were mild to moderate. The mean Cmax was 1.5 µmol and the mean AUC was 2.9 µmol h. Cmax>1.5 µmol was associated with a decrease in standardized uptake value (SUVmax). HSP70 increased substantially following treatment. CONCLUSIONS: This study met its primary end-point. BIIB021 leads to objective responses in refractory GIST patients. Pharmacodynamic studies confirmed HSP90 inhibition. Further evaluation of BIIB021 in GIST is warranted.

An open-label, multicenter, phase II study of bevacizumab for the treatment of angiosarcoma and epithelioid hemangioendotheliomas.

BACKGROUND: To determine efficacy and safety of bevacizumab, a recombinant humanized antibody against vascular endothelial growth factor (VEGF), in the treatment of metastatic or locally advanced angiosarcoma and epithelioid hemangioendotheliomas. PATIENTS AND METHODS: In this single-arm phase II trial, 32 patients were enrolled and they received bevacizumab 15 mg/kg IV infusion in 21-day cycles. Patients had disease that was deemed not surgically resectable, Eastern Cooperative Oncology Group (ECOG) performance status of ≤1, adequate organ function and had not received any radiation treatment in the last 28 days. RESULTS: Of the 30 patients evaluated for efficacy and toxic effect, four (two angiosarcoma and two epithelioid hemangioendothelioma; 17%) had a partial response. Fifteen patients (11 angiosarcoma and 4 epithelioid hemangioendothelioma; 50%) showed stable disease with a mean time to progression of 26 weeks. Bevacizumab was well tolerated with only one grade 4 adverse event. Expected known toxic effects of the drug were manageable. CONCLUSION: Bevacizumab is an effective and well-tolerated treatment for metastatic or locally advanced angiosarcoma and epithelioid hemangioendotheliomas. Further phase III studies of bevacizumab in combination with other chemotherapeutic agents and/or radiation treatment are warranted.

Significant inverse relationship between serum undercarboxylated osteocalcin and glycemic control in maintenance hemodialysis patients.

SUMMARY: Increased levels of serum undercarboxylated osteocalcin, which were associated with bone metabolism markers, correlated inversely with indices of glucose metabolism (plasma glucose, hemoglobin A1C, and glycated albumin) in hemodialysis patients with abnormalities of bone metabolism. INTRODUCTION: Undercarboxylated osteocalcin (ucOC), a possible marker of bone metabolism and one of the osteoblast-specific secreted proteins, has recently been reported to be associated with glucose metabolism. We tested the hypothesis that ucOC levels are associated with indices of glucose metabolism in chronic hemodialysis patients with abnormalities of bone metabolism. METHODS: Serum ucOC, bone alkaline phosphatase (BAP, a bone formation marker), and tartrate-resistant acid phosphatase-5b (TRACP-5b, a bone resorption marker) were measured in 189 maintenance hemodialysis patients (96 diabetics and 93 non-diabetics), and their relationships with glucose metabolism were examined. RESULTS: ucOC correlated positively with BAP (ρ = 0.489, p < 0.0001), TRACP-5b (ρ = 0.585, p < 0.0001) and intact parathyroid hormone (iPTH; ρ = 0.621, p < 0.0001). Serum ucOC levels in the diabetic patients were lower than those of non-diabetic patients (p < 0.001), although there were no significant differences in serum BAP or TRACP-5b between diabetic and non-diabetic patients. Serum ucOC correlated negatively with plasma glucose (ρ = -0.303, p < 0.0001), hemoglobin A1C (ρ = -0.214, p < 0.01), and glycated albumin (ρ = -0.271, p < 0.001), although serum BAP or TRACP-5b did not. In multiple linear regression analysis, log [plasma glucose], log [hemoglobin A1C], and log [glycated albumin] were associated significantly with log [ucOC] after adjustment for age, gender, hemodialysis duration, and body mass index but were not associated with log [BAP], log [TRACP-5b], or log [intact PTH]. CONCLUSION: Increased levels of serum ucOC, which were associated with bone metabolism markers, were inversely associated with indices of glucose metabolism in hemodialysis patients.

Serum adiponectin and bone mineral density in male hemodialysis patients.

SUMMARY: Bone mineral density of the 1/3 distal radius, ultra-distal radius, and lumbar spine correlated significantly and negatively with serum adiponectin. There was a significant positive correlation between serum adiponectin and serum NTX. Thus, adiponectin may play a role in mineral and bone disorder in chronic kidney disease stage 5 dialysis (CKD 5D) patients. INTRODUCTION: Serum adiponectin, an adipocyte-produced hormone, has been reported to correlate negatively with bone mineral density (BMD) in the general population. However, little is known about the association between adiponectin and BMD in patients with CKD. METHODS: BMD of the 1/3 distal and ultra-distal radius, which are enriched with cortical and cancellous bone, respectively, and the lumbar spine was measured by dual X-ray absorptiometry in 114 Japanese male hemodialysis patients (age 61.0 ± 11.1 years; hemodialysis duration 6.6 ± 3.0 years; 43.9% diabetics). Serum total adiponectin, bone formation marker (bone alkaline phosphatase, BAP), and bone resorption marker (cross-linked N-telopeptide of type I collagen (NTX)) were measured. RESULTS: The BMD of the 1/3 distal radius, ultra-distal radius, and lumbar spine correlated significantly and negatively with serum adiponectin level (r = -0.229, p = 0.014; r = -0.286, p = 0.002; r = -0.227, p = 0.013, respectively). In multiple linear regression analyses, serum adiponectin was significantly and independently associated with the BMD of the 1/3 distal radius (R(2) = 0.173, p < 0.001) and ultra-distal radius (R(2) = 0.278, p < 0.001) after adjustment of age, hemodialysis duration, body weight, %fat mass, and log [intact PTH], although it was not with the BMD of the lumbar spine. There was a significant positive correlation between serum adiponectin and serum NTX (r = 0.321, p < 0.001), although there was no significant correlation between serum adiponectin and serum BAP. CONCLUSION: Increased levels of serum adiponectin were associated with decrease in BMD in male hemodialysis patients. Adiponectin may play a role in mineral and bone disorder, possibly in bone resorption, of patients with CKD 5D.

Effect of cinacalcet on bone mineral density of the radius in hemodialysis patients with secondary hyperparathyroidism.

BACKGROUND/AIM: Cinacalcet, an allosteric modulator of the calcium sensing receptor, effectively reduces serum parathyroid hormone (PTH) in patients with secondary hyperparathyroidism. It is not well known whether bone mineral density (BMD) of hemodialysis patients with secondary hyperparathyroidism is altered after cinacalcet treatment. METHODS: The BMD in the distal 1/3 of the radius and in the ultradistal radius, which are enriched with cortical and cancellous bone, respectively, was examined by dual X-ray absorptiometry, 1 year prior to, at the start, and 1 year after cinacalcet treatment, in 61 patients. RESULTS: The BMD of both the distal 1/3 and ultradistal radius decreased significantly in the year prior to cinacalcet treatment (p < 0.01). However, the BMD at either site did not change significantly in the year after cinacalcet treatment. The annual changes in the BMD of the distal 1/3 radius increased significantly from -0.023 ± 0.029 g/cm2/year to -0.002 ± 0.033 g/cm2/year, prior to and after cinacalcet treatment, respectively; however, the annual changes in the BMD of the ultradistal radius did not change significantly prior to and after cinacalcet treatment. CONCLUSION: There was a significant association between cinacalcet treatment and reduction in BMD loss in patients with secondary hyperparathyroidism. Cortical bone, rather than cancellous bone, was particularly affected by cinacalcet treatment.

Reduction of whole PTH/intact PTH ratio as a predictor of bone metabolism in cinacalcet treatment of hemodialysis patients with secondary hyperparathyroidism.

UNLABELLED: In cinacalcet treatment of hemodialysis (HD) patients with secondary hyperparathyroidism (SHPT), not only intact parathyroid hormone (I-PTH), whole PTH (W-PTH), and bone markers, but also W-PTH/I-PTH ratio as proportion of active PTH(1-84) molecules were decreased. Changes in W-PTH/I-PTH ratio significantly correlated and predicted changes in bone marker. INTRODUCTION: Cinacalcet partly suppresses the secretion of PTH by enhancing PTH(1-84) degradation into N-truncated fragments. The objectives of this study is to investigate the significance of the N-truncated PTH/PTH(1-84) ratio for the prediction of the effect of cinacalcet in HD patients. METHODS: Serum parameters were measured during 12 weeks of oral cinacalcet administration at 25 mg daily in 39 HD patients with SHPT. RESULTS: Serum Ca, Pi, W-PTH, I-PTH, and W-PTH/I-PTH ratio all decreased significantly in a time-dependent manner during cinacalcet administration. Serum tartrate-resistant acid phosphatase (TRAP) 5b reflected these changes more precisely than serum N-telopeptide of type-I collagen. At 1 week, changes in I-PTH and W-PTH correlated significantly with those in serum Pi, but not Ca. Changes in serum Pi (but not Ca) and serum W-PTH also correlated significantly with changes in serum TRAP5b at both 4 and 12 weeks, while changes in serum I-PTH correlated significantly with those in serum TRAP5b only at 12 weeks. Changes in the serum W-PTH/I-PTH ratio correlated significantly with those in serum TRAP5b at both 4 and 12 weeks, and changes in serum W-PTH/I-PTH ratio at 4 weeks showed a tendency for a correlation with changes in serum TRAP5b at 12 weeks. HD patients with a reduced W-PTH/I-PTH ratio after 4 weeks had a significantly greater reduction of TRAP5b over 12 weeks. CONCLUSION: W-PTH and the W-PTH/I-PTH ratio allow estimation of the potency of cinacalcet in enhancement of PTH degradation, and thus no less reliable markers than I-PTH for reflecting cinacalcet-induced bone resorption.

Poor muscle quality rather than reduced lean body mass is responsible for the lower serum creatinine level in hemodialysis patients with diabetes mellitus.

BACKGROUND: The serum creatinine level is significantly lower in well-nourished hemodialysis patients with diabetes mellitus (DM) than in their non-DM counterparts, despite the presence of anuria in these patients. The factors associated with this finding have not been determined. PATIENTS AND METHODS: We evaluated the association of serum creatinine with handgrip strength (HGS) and lean body mass index (LMI) in a cross-sectional study of 102 DM and 208 non-DM hemodialysis patients to determine if poorer muscle quality in DM patients could explain the reduced level of serum creatinine. All the DM patients were well-nourished. Grip dynamometry and dual-energy X-ray absorptiometry (DXA) were used to measure HGS and LMI, respectively. RESULTS: The DM patients had a significantly lower serum creatinine level and HGS compared to the non-DM patients, but whole-body LMI and LMI of the upper limbs did not differ between the two groups of patients. The DM patients had significantly lower serum creatinine/whole-body LMI, serum creatinine/arm LMI, HGS/whole-body LMI, and HGS/arm LMI ratios. The serum creatinine level was significantly correlated with HGS and with whole-body and upper limb LMI in both groups of patients. However, regression analyses of LMI with serum creatinine and HGS gave significantly shallower slopes for the DM patients compared to the non-DM patients. CONCLUSION: This suggests that the muscle strength generated per unit of muscle mass, which is reflected well by the serum creatinine level, is significantly reduced in DM hemodialysis patients. Therefore, our results show that the significantly lower serum creatinine levels in DM hemodialysis patients compared to non-DM hemodialysis patients may be explained by poor muscle quality rather than by reduced muscle mass or malnutrition.

Glycemic control and survival of diabetic hemodialysis patients--importance of lower hemoglobin A1C levels.

AIMS: The significance of hemoglobin A1C (HbA1C) on the survival of diabetic hemodialysis patients still remains controversial. We investigated the impact of HbA1C on the survival. METHODS: A total of 122 diabetic patients on maintenance hemodialysis (age, 59.9+/-11.9 years [mean+/-SD]; hemodialysis duration: 53+/-38 months) were surveyed (survey period: 46+/-19 months). RESULTS: The cumulative survival of the poor glycemic control group (mean HbA1C of 3-month period > or =6.3%, n=62) was significantly lower than that of the good group (HbA1C<6.3%, n=60), as determined by Kaplan-Meier estimation (P=0.0084, log-rank test). Kaplan-Meier analysis also demonstrated that both cardiovascular and non-cardiovascular mortalities were higher in the poor group than in the good group (P=0.0545 and P=0.0453, respectively). In a multivariate Cox proportional hazard model, the mean HbA1C was a significant predictor of survival (OR 1.260 per 1.0%, 95% CI 1.020-0.579, P=0.0325). CONCLUSIONS: Poor glycemic control is an independent predictor of poor prognosis in diabetic hemodialysis patients. HbA1C is a clinically useful parameter for identifying the risk for mortality, both for cardiovascular and non-cardiovascular mortality, and that careful management of glycemic control by use of HbA1C is important.

Significant association between the presence of peripheral vascular calcification and lower serum magnesium in hemodialysis patients.

AIM: Vascular calcification, which significantly increases cardiovascular and other causes of mortality, is highly prevalent in hemodialysis patients. The aim of the present study was to examine the association between serum magnesium levels and vascular calcification in hemodialysis patients. METHODS: 390 nondiabetic patients on maintenance hemodialysis (226 males and 164 females, 59 +/- 13 years) were examined. Hand roentgenography was performed in each patient, and visible vascular calcification of the hand arteries was evaluated. Blood was drawn to measure serum calcium, phosphate, magnesium and intact parathyroid hormone levels. RESULTS: There were 52 patients (38 males and 14 females) with vascular calcification, and 338 (188 males and 150 females) without. Serum phosphate was significantly higher in the former compared with the latter group (p < 0.005); serum intact parathyroid hormone was significantly higher (p < 0.05), whereas serum calcium was not statistically different between the two groups. Serum magnesium was significantly lower in patients with vascular calcification than in those without (2.69 +/- 0.28 vs. 2.78 +/- 0.33 mg/dl, p < 0.05). Multivariate logistic regression analysis revealed that serum magnesium concentration was a significant independent factor associated with the presence of vascular calcification in hemodialysis patients (odds ratio 0.28, 95% CI 0.09 - 0.92/1 mg/dl increase in serum magnesium, p = 0.036) after adjustment for age, gender, duration of hemodialysis, calcium, phosphate and intact parathyroid hormone concentrations. CONCLUSION: Hypomagnesemia is significantly associated with the presence of vascular calcification of the hand arteries, independent of serum calcium and phosphate levels. These results suggest that higher serum magnesium concentrations may play an important protective role in the development of vascular calcification in hemodialysis patients, and that magnesium concentration of dialysis fluid may be reconsidered in view of preventing vascular calcification in hemodialysis patients.

Bizarre big belly ball: intraabdominal abscess mimicking stauffer syndrome secondary to uterine leiomyosarcoma.

BACKGROUND: Stauffer syndrome, a very rare paraneoplastic syndrome, refers to reversible intrahepatic cholestasis in the setting of an abdominal malignancy. CASE: A 60-year-old female with a past medical history of uterine leiomyosarcoma status post radical hysterectomy, presented three months later with right upper quadrant abdominal pain. Laboratory evaluation revealed intrabdominal cholestasis and ultrasound of the abdomen showed an echogenic solid mass consistent with a metastatic leiomyosarcoma, and it was felt that her hyperbilirubinemia was due to Stauffer syndrome. However, three days later, blood culture grew gram negative bacilli, and CT scan of the abdomen revealed multiple mesenteric masses with air bubbles consistent with an abdominal abscess. The abscess was drained under CT-scan guidance and her cholestasis gradually came back to nearly normal. CONCLUSION: The case highlights the importance of considering infectious etiologies and Stauffer syndrome in the differential diagnosis of liver dysfunction in patients with intraabdominal malignancies.

Development of multidrug resistance type I Cmdr1 expression in chicken embryonic gonads.

A primary role of P-glycoprotein (P-gp), encoded by the multidrug resistance type I gene, is to protect against naturally occurring xenotoxics. Recently, the preferential expression of chicken multidrug resistance type I (Cmdr1) was identified in the embryonic gonads during the early periods of development. Here we investigated the expression of Cmdr1 and P-gp in the gonads during embryogenesis, and compared to that in the ovarian follicles of domestic hens (Gallus gallus). As revealed by immunohistochemistry, P-gp was highly expressed in theca cells of mature follicles, whereas the expression was low in immature follicles. Immunohistochemical analysis showed that expression of Cmdr1-type P-gp was very low in embryonic gonads. Cmdr1 mRNA was undetectable in the gonads of 5-day embryos (E5) by RT-PCR, whereas Cmdr1 mRNA was significantly detectable in the developing gonads at E9 and E21. In the testicular tissues, germ cells were distributed along developing seminiferous cords as identified by a specific marker gene, whereas Cmdr1-type P-gp positive cells were observed evenly on testicular tissues. Collectively, it is concluded that Cmdr1 expression is initiated in the chicken ovary and testis after sexual differentiation, but expression of Cmdr1-type P-gp is very low through embryogenesis.

Role of fibroblast growth factor-23 in peripheral vascular calcification in non-diabetic and diabetic hemodialysis patients.

INTRODUCTION: Fibroblast growth factor (FGF) 23 is a recently identified circulating factor that regulates phosphate (Pi) metabolism. Since the derangement of Pi control is an important risk factor for vascular calcification, we investigated the importance of plasma FGF-23 in the development of vascular calcification in the aorta and peripheral artery in hemodialysis patients with and without diabetes mellitus (DM). METHODS: Male hemodialysis patients with DM (n=32) and without DM (n=56) were examined. Plasma samples were obtained before the start of dialysis sessions, and the FGF-23 levels were determined by enzyme-linked immunosorbent assay. Roentgenography of the aorta and hand artery was performed, and visible vascular calcification was evaluated by one examiner, who was blinded to the patient characteristics. RESULTS: In the 56 non-DM hemodialysis patients, vascular calcification was found in the hand artery in 5 patients (8.9%) and in the aorta in 23 patients (41.1%). These levels were significantly lower (p<0.05) than in the 32 DM patients, of whom, 19 (59.4%) and 21 (65.6%) had vascular calcification of the hand artery and aorta, respectively. Multiple regression analyses performed separately in the non-DM and DM patients showed that the plasma FGF-23 level, CaxPi product, and body weight are independent factors significantly associated with hand-artery calcification and that diastolic blood pressure is associated with aorta calcification in non-DM patients. In DM patients, the plasma FGF-23 level and hemodialysis duration emerged as independent factors associated with hand-artery calcification and diastolic blood pressure was associated with aorta calcification. The independent association of the plasma FGF-23 level with hand-artery calcification was retained in both non-DM and DM patients when adjusted for the CaxPi product. CONCLUSION: Our findings show that the plasma FGF-23 level is an independent factor negatively associated with peripheral vascular calcification in the hand artery, but not in the aorta, in both male non-DM and DM hemodialysis patients, even when adjusted for the CaxPi product. This study raises the possibility that the plasma FGF-23 level may provide a reliable marker for Moenckeberg's medial calcification in male hemodialysis patients, independent of its regulatory effect on Pi metabolism.