Nephrogenic systemic fibrosis (NSF) is a clinical syndrome linked with exposure in renal failure patients to gadolinium-based magnetic resonance imaging contrast agents (GBCAs). The pathogenesis of ...the disease is largely unknown. The present study addresses potential pathophysiological mechanisms.
Here, we have examined human skin in organ culture and human dermal fibroblasts in monolayer culture for responses to GBCA stimulation.
Treatment of normal human skin in organ culture with Omniscan had no significant effect on type I procollagen but increased both matrix metalloproteinase-1 and tissue inhibitor of metalloproteinases-1. At the histologic level, many interstitial cells demonstrated cytologic features characteristic of activation (ie, light staining, oblong, plump nuclei). Omniscan, as well as 3 other magnetic resonance imaging contrast agents (Magnevist, Multihance, and Prohance), increased proliferation of human dermal fibroblasts in monolayer culture. Increased proliferation was accompanied by an increase in production of both matrix metalloproteinase-1 and tissue inhibitor of metalloproteinases-1 but no increase in type I procollagen. Concentrations required for effects differed among the 4 agents (Omniscan < Magnevist and Multihance < Prohance). In contrast to its effects on fibroblast function, Omniscan did not stimulate human epidermal keratinocyte proliferation when examined over a wide range of concentrations.
These data provide evidence that GBCA exposure in ex vivo skin from healthy individuals increases fibroblast proliferation and has effects on the enzyme/inhibitor system that regulates collagen turnover in the skin.
Background
Identifying pancreatic cancer patients at high risk of early mortality following pancreaticoduodenectomy (PD) is important for treatment decisions in a multidisciplinary setting. This ...study examines the preoperative predictors of early mortality following PD and combines these variables into an early mortality risk score (EMRS).
Methods
Medical records of patients who underwent PD for pancreatic adenocarcinoma at the Johns Hopkins Hospital between 30 August 1993 and 28 February 2005 were reviewed. Cox proportional hazards analysis was performed to identify predictors of early mortality, defined as death at 9 and 12 months. EMRS was constructed from univariate associated risk factors (age >75 years, tumor size ≥3cm, poor differentiation, co-morbid diseases) with each factor assigned 1 point (range of 0-4). EMRS was evaluated as an independent predictor of death at 9 and 12 months.
Results
On univariate analysis, risk factors for death at 9 months included age ≥75 years (RR, 1.6;
p
= .009), comorbid disease (RR, 1.5;
p
= 0.020), tumor ≥3 cm (RR, 1.4;
P
= 0.050), and poor differentiation (RR, 2.1;
P
< 0.001). EMRS was associated with early mortality among those who did (
p
= 0.038) and did not receive adjuvant treatment (
p
< 0.001). A modified EMRS without tumor differentiation was also associated with early mortality (
p
< 0.001). Results persisted when reanalyzed using death at 12 months.
Conclusions
EMRS may identify patients at risk of early mortality following PD who may be candidates for alternatively sequenced treatment protocols. Prospective validation of this EMRS is needed.
Intraductal papillary mucinous neoplasms are mucin-producing cystic neoplasms of the pancreas. One-third are associated with invasive carcinoma. We examined the benefit of adjuvant chemoradiotherapy ...(CRT) for this cohort.
Patients who had undergone pancreatic resection at Johns Hopkins Hospital between 1999 and 2004 were reviewed. Of these patients, 83 with a resected pancreatic mass were found to have an intraductal papillary mucinous neoplasm with invasive carcinoma, 70 of whom met inclusion criteria for the present analysis.
The median age at surgery was 68 years. The median tumor size was 3.3 cm, and invasive carcinoma was present at the margin in 16% of the patients. Of the 70 patients, 50% had metastases to the lymph nodes and 64% had Stage II disease. The median survival was 28.0 months, and 2- and 5-year survival rate was 57% and 45%, respectively. Of the 70 patients, 40 had undergone adjuvant CRT. Those receiving CRT were more likely to have lymph node metastases, perineural invasion, and Stage II-III disease. The 2-year survival rate after surgery with vs. without CRT was 55.8% vs. 59.3%, respectively (p = NS). Patients with lymph node metastases or positive surgical margins benefited significantly from CRT (p = .047 and p = .042, respectively). On multivariate analysis, adjuvant CRT was associated with improved survival, with a relative risk of 0.43 (95% confidence interval, 0.19-0.95; p = .044) after adjusting for major confounders.
Adjuvant CRT conferred a 57% decrease in the relative risk of mortality after pancreaticoduodenectomy for intraductal papillary mucinous neoplasms with an associated invasive component after adjusting for major confounders. Patients with lymph node metastases or positive margins appeared to particularly benefit from CRT after definitive surgery.
Purpose
To assess the frequency with which previously reported characteristic findings of retroperitoneal fibrosis (RPF) (a circumferential or almost circumferential peri-aortic mass centered at L4, ...which does not displace the abdominal aorta or proximal common iliac arteries) are present in patients with RPF, in patients with other fibrosing diseases, and in cancer patients referred to a subspecialty clinic with a suspected diagnosis of RPF, in order to determine whether diagnostic percutaneous biopsy can be avoided in some patients.
Methods
This HIPAA-compliant Institutional Review Board-approved retrospective study assessed clinical and CT and MR imaging abnormalities on imaging studies in 92 patients referred to a subspecialty clinic with suspected RPF over a 14-year period. Two reviewers, in consensus, determined the frequency of different CT and MRI findings in three groups of patients (Group 1: those with an eventual diagnosis of RPF, Group 2: those with a fibrosing disease associated with vascular or urologic abnormalities, and Group 3: those with cancer). Assessed imaging features included the presence of retroperitoneal masses, whether masses were single or multiple, whether such masses were circumferential or nearly circumferential, whether they displaced the aorta away from the spine (with the degree of such displacement measured), and whether there were abnormalities outside of the peri-aortic region of the retroperitoneum. The frequency with which findings previously reported as characteristic of RPF were present was determined for each of the three groups. Imaging results were correlated with the final diagnoses.
Results
Of 68 subjects eventually diagnosed with retroperitoneal fibrosis (RPF) (Group 1), 47 had peri-aortic retroperitoneal masses, 18 of which displaced the aorta anteriorly away from the spine. Of 12 subjects with fibrosing abnormalities related to vascular or urologic disease (Group 2), six had retroperitoneal masses, none of which displaced the aorta away from the spine. Of 12 subjects with malignancies (Group 3), six had peri-aortic retroperitoneal masses only two of whom had aortic displacement. Only 34 of 68 Group 1 subjects had peri-aortic masses characteristic of RPF, compared with six Group 2 subjects and one Group 3 subject. Subjects with characteristic retroperitoneal masses were significantly more likely to have benign disease than cancer (
p
= 0.009).
Conclusion
Many patients with RPF do not have characteristic imaging findings. Contrary to prior publications, absence of aortic displacement is not seen in all patients with RPF and is seen in some cancer patients. Nonetheless, when infiltrative peri-aortic retroperitoneal soft tissue that does not displace the aorta is encountered on CT or MRI, RPF can be diagnosed with a high degree of confidence, obviating the need for biopsy.
Failed alveolar formation and excess, disordered elastin are key features of neonatal chronic lung disease (CLD). We previously found fewer alveoli and more elastin in lungs of preterm compared with ...term lambs that had mechanical ventilation (MV) with O(2)-rich gas for 3 wk (MV-3 wk). We hypothesized that, in preterm more than in term lambs, MV-3 wk would reduce lung expression of growth factors that regulate alveolarization (VEGF, PDGF-A) and increase lung expression of growth factors transforming growth factor (TGF)-alpha, TGF-beta(1) and matrix molecules (tropoelastin, fibrillin-1, fibulin-5, lysyl oxidases) that regulate elastin synthesis and assembly. We measured lung expression of these genes in preterm and term lambs after MV for 1 day, 3 days, or 3 wk, and in fetal controls. Lung mRNA for VEGF, PDGF-A, and their receptors (VEGF-R2, PDGF-Ralpha) decreased in preterm and term lambs after MV-3 wk, with reduced lung content of the relevant proteins in preterm lambs with CLD. TGF-alpha and TGF-beta(1) expression increased only in lungs of preterm lambs. Tropoelastin mRNA increased more with MV of preterm than term lambs, and expression levels remained high in lambs with CLD. In contrast, fibrillin-1 and lysyl oxidase-like-1 mRNA increased transiently, and lung abundance of other elastin-assembly genes/proteins was unchanged (fibulin-5) or reduced (lysyl oxidase) in preterm lambs with CLD. Thus MV-3 wk reduces lung expression of growth factors that regulate alveolarization and differentially alters expression of growth factors and matrix proteins that regulate elastin assembly. These changes, coupled with increased lung elastase activity measured in preterm lambs after MV for 1-3 days, likely contribute to CLD.
Background
There are limited data on patterns of recurrence and factors associated with local recurrence following pancreaticoduodenectomy for pancreatic adenocarcinoma and adjuvant ...5-flurouracil-based chemoradiation therapy.
Methods and Materials
Between 1995 and 2005, 905 patients underwent pancreaticoduodenectomy for pancreatic adenocarcinoma; 154 patients had complete pattern of recurrence data available.
Results
At median follow-up of 20.2 months, 103 (66.9%) patients recurred with median time to recurrence of 16.2 months. Most patients recurred with distant disease only (68.9%), while 21.4% patients recurred with local disease only; ten (9.7%) patients recurred with local and distant disease. Several factors were associated with local recurrence: poor tumor differentiation (hazards ration HR 2.39) and presence of metastatic lymph nodes (HR 1.89, both
p
< 0.05). Among N1 patients, poor tumor differentiation (HR 3.92), >5 metastatic LN (HR 3.75), and lymph node ratio (LNR) >0.4 (HR 2.96) had the highest risk of local recurrence (all
p
< 0.05). Increasing LNR was associated with an incremental increased risk of local recurrence (LNR <0.2, 21.3% versus LNR ≥0.2 to 0.4, 25.2% versus LNR >0.4, 40.4%;
p
< 0.05).
Conclusions
Although most patients who receive standard 5-flurouracil-based chemoradiation therapy will ultimately succumb to distant disease, about 30% recur locally. Poor tumor differentiation, a high number of metastatic LN (>5), and LNR >0.4 are associated with the highest risk of local failure. In these patients, radiation dose escalation and/or a combination of radiation with novel chemotherapeutic agents may be necessary to improve outcomes.
We describe 2 patients with perivascular low-attenuation soft tissue and inflammatory changes surrounding the coronary arteries in the clinical setting of idiopathic retroperitoneal fibrosis. Neither ...patient had inducible ischemia on cardiac stress testing. The coronary arteries present an additional site of interest as connections between sclerosing diseases--including retroperitoneal fibrosis, fibrosing mediastinitis, autoimmune pancreatitis, sclerosing cholangitis, and other entities--continue to emerge.
Palliative care Moss, Alvin H; Holley, Jean L; Davison, Sara N ...
American journal of kidney diseases,
January 2004, 2004, 2004-Jan, 2004-01-00, 20040101, Letnik:
43, Številka:
1
Journal Article
PDF
