Reducing glucocorticoid dosage improves serum osteocalcin in patients with rheumatoid arthritis-results from the TOMORROW study.

UNLABELLED: Decreasing the daily dose of glucocorticoids improved bone metabolic marker levels in patients with rheumatoid arthritis. However, changes in disease activity did not influence bone metabolism. Bone metabolism might thus remain uncontrolled even if disease activity is under good control. Decreasing glucocorticoid dosage appears important for improving bone metabolism. INTRODUCTION: Patients with rheumatoid arthritis (RA) develop osteoporosis more frequently than healthy individuals. Bone resorption is increased and bone formation is inhibited in patients with RA, and glucocorticoid negatively affects bone metabolism. We aimed to investigate factors influencing bone metabolic markers in patients with RA. METHODS: We started the 10-year prospective cohort Total Management of Risk Factors in Rheumatoid Arthritis Patients to Lower Morbidity and Mortality (TOMORROW) study in 2010. We compared changes in urinary cross-linked N-telopeptide of type I collagen (uNTx) and serum osteocalcin (OC), as markers of bone resorption and formation, respectively, in 202 RA patients and age- and sex-matched volunteers between 2010 and 2011. We also investigated factors influencing ΔuNTx and ΔOC in the RA group using multivariate analysis. RESULTS: Values of ΔuNTx were significantly lower in patients with RA than in healthy controls (-0.51 vs. 7.41 nmol bone collagen equivalents (BCE)/mmol creatinine (Cr); p = 0.0013), whereas ΔOC values were significantly higher in RA patients (0.94 vs. 0.37 ng/ml; p = 0.0065). Changes in prednisolone dosage correlated negatively with ΔOC (ß = -0.229, p = 0.001), whereas changes in disease activity score, bisphosphonate therapy, and period of biologics therapy did not correlate significantly with ΔOC. No significant correlation was seen between ΔuNTx and change in prednisolone dosage. CONCLUSIONS: Decreased glucocorticoid dosage improved bone metabolic markers in RA, but disease activity, bisphosphonate therapy, and period of biologics therapy did not influence levels of bone metabolic markers. Decreasing glucocorticoid dosage appears important for improving bone metabolic marker profiles in patients with RA.

How the lumbrical muscle contributes to placing the fingertip in space: a three dimensional cadaveric study to assess fingertip trajectory and metacarpophalangeal joint balancing.

Three-dimensional fingertip trajectory was examined under different force levels of the lumbrical muscle to clarify the function of the lumbrical muscle in free index finger motion. The metacarpophalangeal joint balancing effect of the lumbrical muscle in the thumb-up position was also examined. The motions of the finger bones were recorded during simulated contraction of flexor digitorum profundus when different forces (0.000-1.960 N) were applied to the lumbrical muscle in cadaveric specimens. The greater the force with which the lumbrical muscle was pulled, the larger the arc formed by the fingertip, and the greater the rebalancing influence on the metacarpophalangeal joint. This result indicates that the lumbrical muscle functions simultaneously to enlarge the fingertip trajectory and to balance the metacarpophalangeal joint against gravity in the axial plane. A 0.980 N force was ideal for maximal finger movement. The lumbrical muscle rebalanced the metacarpophalangeal joint against gravity in the thumb-up position with a force ⩾0.980 N.

Prognostic nomogram for nonresectable pancreatic cancer treated with gemcitabine-based chemotherapy.

BACKGROUND: A nomogram is progressively being used as a useful predictive tool for cancer prognosis. A nomogram to predict survival in nonresectable pancreatic cancer treated with chemotherapy has not been reported. METHODS: Using prospectively collected data on patients with nonresectable pancreatic cancer receiving gemcitabine-based chemotherapy at five Japanese hospitals, we derived a predictive nomogram and internally validated it using a concordance index and calibration plots. RESULTS: In total, 531 patients were included between June 2001 and February 2013. The American Joint Committee on Cancer (AJCC) TNM stages were III and IV in 204 and 327 patients, respectively. The median survival time of the total cohort was 11.3 months. A nomogram was generated to predict survival probabilities at 6, 12, and 18 months and median survival time, based on the following six variables: age; sex; performance status; tumour size; regional lymph node metastasis; and distant metastasis. The concordance index of the present nomogram was higher than that of the AJCC TNM staging system at 12 months (0.686 vs 0.612). The calibration plots demonstrated good fitness of the nomogram for survival prediction. CONCLUSIONS: The present nomogram can provide valuable information for tailored decision-making early after the diagnosis of nonresectable pancreatic cancer.

A multicentre randomised phase II trial of gemcitabine alone vs gemcitabine and S-1 combination therapy in advanced pancreatic cancer: GEMSAP study.

BACKGROUND: This randomised phase II trial compared gemcitabine alone vs gemcitabine and S-1 combination therapy in advanced pancreatic cancer. METHODS: Patients were randomly assigned to 4-week treatment with gemcitabine alone (1000, mg m(-2) gemcitabine by 30-min infusion on days 1, 8, and 15) or gemcitabine and S-1 combination therapy (1000, mg m(-2) gemcitabine by 30-min infusion on days 1 and 15 and 40 mg m(-2) S-1 orally twice daily on days 1-15). The primary end point was progression-free survival (PFS). RESULTS: Between July 2006 and February 2009, 106 patients were enrolled. The PFS in gemcitabine and S-1 combination arm was significantly longer than in gemcitabine arm (5.4 vs 3.6 months), with a hazard ratio of 0.64 (P=0.036). Overall survival (OS) for gemcitabine and S-1 combination was longer than that for gemcitabine monotherapy (13.5 vs 8.8 months), with a hazard ratio of 0.72 (P=0.104). Overall, grade 3 or 4 adverse events were similar in both arms. CONCLUSION: Gemcitabine and S-1 combination therapy demonstrated longer PFS in advanced pancreatic cancer. Improved OS duration of 4.7 months was found for gemcitabine and S-1 combination therapy, though this was not statistically significant.

Inhibition of renin-angiotensin system affects prognosis of advanced pancreatic cancer receiving gemcitabine.

BACKGROUND: The renin-angiotensin system (RAS) is thought to have a role in carcinogenesis, and RAS inhibition may prevent tumour growth. METHODS: We retrospectively investigated the impact of angiotensin I-converting enzyme inhibitors (ACEIs) and angiotensin II type-1 receptor blockers (ARBs) in 155 patients with pancreatic cancer receiving gemcitabine monotherapy. Patients were divided into three groups: the ACEI/ARB group (27 patients receiving an ACEI or ARB for hypertension (HT)), the non-ACEI/ARB with HT group (25 patients receiving antihypertensive drugs other than ACEIs or ARBs), and the non-HT group (103 patients receiving no antihypertensive drugs). RESULTS: Patient characteristics were not different, except for age and HT medications. Progression-free survival (PFS) was 8.7 months in the ACEI/ARB group, 4.5 months in the non-ACEI/ARB with HT group, and 3.6 months in the non-HT group. Overall survival (OS) was 15.1 months in the ACEI/ARB group, 8.9 months in the non-ACEI/ARB with HT group, and 9.5 months in the non-HT group. The use of ACEIs/ARBs was a significant prognostic factor for both PFS (P=0.032) and OS (P=0.014) in the multivariate analysis. CONCLUSIONS: The ACEIs/ARBs in combination with gemcitabine might improve clinical outcomes in patients with advanced pancreatic cancer. Prospective trials are needed to test this hypothesis.

Laboratory and imaging features of kidney involvement in autoimmune pancreatitis: incidence, correlation, and steroid therapy response.

AIM: Autoimmune pancreatitis (AIP) is a rare subtype of chronic pancreatitis. AIP has been suggested to be complicated by tubulointerstitial nephritis or glomerulonephritis, implying that the kidney is involved as a phenotype of IgG4-positive multi-organ lymphoproliferative syndrome; however, the clinical significance of this novel entity is not well-defined. METHODS: We conducted a retrospective cohort analysis of 47 (male, 39; female, 8) AIP patients. RESULTS: The patients (mean age, 70.3 +/- 9.5 years) had a mean observation period of 4.1 years. Before treatment, renal dysfunction with an eGFR of 30 and 15 ml/min/1.73 m2 developed only in 10.6% (5/47) and 2.1% (1/47) of the patients, respectively. Nevertheless, urinary N-acetyl-beta-D-glucosaminidase and alpha1-microglobulin levels were elevated in 78.6% (11/14) and 30.8% (4/13) of the patients, respectively. Renal involvement in contrast-enhanced CT imaging was present in 18.2% (8/44) of the patients and was associated with proteinuria (p = 0.04) and a decrease in eGFR (p < 0.01). Furthermore, a follow-up CT study (mean, 545 days) revealed improved kidney lesions in 80.0% (4/5) of the patients after oral corticosteroid administration. In contrast, first-time kidney involvements appeared newly in 3.6% (1/28) of the patients after steroid therapy for nonrenal AIP symptoms, and in 14.3% (1/7) of the patients under no specific therapy (p = 0.02). CONCLUSION: Although severe renal failure develops rarely in AIP patients, renal abnormalities have been significantly detected by biochemical and radiological tests. Oral corticosteroid administration, even when not targeting symptomatic nephropathy, can treat and prevent kidney involvements in AIP.

An incidentally discovered small and asymptomatic para-aortic paraganglioma.

Preoperative diagnosis of asymptomatic paraganglioma is difficult due to the lack of specific symptoms. In this report, we present a rare case of a small and asymptomatic para-aortic paraganglioma. A 34-year-old woman who complained of back pain was admitted for further examination. No abnormal findings were observed on physical or laboratory examinations. An abdominal CT scan and an abdominal MRI incidentally noted a mass about 3 cm in diameter adjacent to the right edge of the inferior vena cava. The following aortic angiography showed the tumor with a feeding artery diverting directly from the aorta. The tumor was completely resected by laparotomy. The resected tumor, 3 x 3 x 3 cm in size, was soft, dark-reddish and encapsulated. Immunohistochemical examinations showed that it was positive for neuron-specific enolase, chromogranin A and adrenocorticotropin. Under these findings, the diagnosis of para-aortic paraganglioma was determined. Seven years after the operation, she remains asymptomatic and free of disease.

Self-expandable metallic stents for malignant biliary obstruction with an anomalous pancreaticobiliary junction.

BACKGROUND: Anomalous pancreaticobiliary junction (APBJ) is associated with pancreaticobiliary cancer. Limited data are available on endoscopic biliary drainage for unresectable malignant biliary obstruction with APBJ. This study evaluated the efficacy and safety of self-expandable metallic stents (EMSs) for the management of malignant biliary obstruction with APBJ. METHODS: Between 1993 and 2005, 324 patients with unresectable malignant biliary obstruction underwent insertion of an EMS. Six of these patients with concomitant APBJ constituted the subjects of this study. Early (30 days after EMS insertion) stent-related complications and stent patency were evaluated in these six patients. RESULTS: The cause of biliary obstruction was gallbladder cancer in four patients and pancreatic cancer in two patients. Uncovered EMSs were inserted across the common channel without performance of a biliary sphincterotomy. The diameter of the uncovered EMS used was based on the diameter of the common channel. For all six patients, endoscopic biliary drainage was successful, and their jaundice subsided steadily. None of the six patients experienced early complications, including acute pancreatitis. The mean stent-related complication-free period was 163 days. Stent occlusion caused by tumor ingrowth occurred in two patients. Acute cholangitis and cholecystitis were observed in one patient each. CONCLUSIONS: Uncovered EMSs are effective for palliation of unresectable malignant biliary obstruction in patients who have APBJ without increasing the risk of stent-related early complications.

Endoscopic transpapillary approach to the gallbladder for diagnosing gallbladder cancer.

PURPOSE: Gallbladder cancer (GBC) has a poor prognosis that is related to delayed diagnosis. The present study evaluated the efficacy of the transcystic ductal approach in diagnosing GBC. METHODS: A catheter was introduced into the gallbladder endoscopically via the cystic duct to obtain bile for cytology. Subsequently, cytology specimens were collected using a brush, and intraductal ultrasonography (IDUS) was performed using a miniature probe in patients suspected of having GBC. RESULTS: Bile cytology was performed successfully in 23 of 25 patients (92%). The sensitivity, specificity and accuracy of cytology were 44.4%, 100% and 78.3%, respectively. Brush cytology and IDUS were successful in six of eight (75%) and nine of 15 (60%) patients, respectively. Brush cytology was positive in two of five patients with GBC. In all four patients with invasive cancer, IDUS showed an irregularity or disruption of the outermost hyperechoic layer. CONCLUSIONS: The endoscopic transpapillary approach to the gallbladder was useful for the diagnosis of GBC. Brush cytology and IDUS may improve diagnostic efficacy and provide more useful information.