Idiopathic retroperitoneal fibrosis (IRPF) is an increasingly recognized syndrome. The development of inflammation and fibrosis in the retroperitoneum most often results in a periaortic mass on ...computed tomography or magnetic resonance imaging that causes pain and constitutional symptoms. Its organ involvement results in urinary tract obstruction, bowel dysfunction, and venous compression with leg swelling, or thrombosis. The syndrome appears autoimmune in nature, but has no specific immunologic markers. However, nonspecific inflammatory indicators, such as sedimentation rate and C-reactive protein level, reflect disease activity and therapeutic response. Retroperitoneal fibrosis also can arise secondary to inflammatory, infectious, or malignant disease in retroperitoneal organs, in which case treatment is directed at the primary process. However, in patients with IRPF, initial treatment of the local mechanical complications must be followed by medical therapy with corticosteroids or, more recently, the addition of steroid-sparing agents. Although there are no controlled therapeutic trials, a number of reports with as few as 3 or as many as 28 cases describe sustained and effective steroid-sparing treatment with cyclophosphamide, azathioprine or colchicine, or such newer agents as mycophenolate mofetil or tamoxifen. Overall, IRPF responds to corticosteroid therapy initially but recurs without prolonged treatment. Sustained remission can be attained with steroid-sparing treatment. Kidney function can be preserved, and local organ dysfunction can remit for periods of 10 years or more. Although not randomized or controlled, the evidence convincingly supports a combination of initial surgical or urological intervention, along with early corticosteroid therapy for up to 6 months followed by either mycophenolate or tamoxifen for 1 to 3 years. What was previously believed to be an uncommon and challenging syndrome can be treated successfully when recognized by its characteristic presentation.
The authors investigated the incidence and risk factors for postoperative acute renal failure after major noncardiac surgery among patients with previously normal renal function.
Adult patients ...undergoing major noncardiac surgery with a preoperative calculated creatinine clearance of 80 ml/min or greater were included in a prospective, observational study at a single tertiary care university hospital. Patients were followed for the development of acute renal failure (defined as a calculated creatinine clearance of 50 ml/min or less) within the first 7 postoperative days. Patient preoperative characteristics and intraoperative anesthetic management were evaluated for associations with acute renal failure. Thirty-day, 60-day, and 1-yr all-cause mortality was also evaluated.
A total of 65,043 cases between 2003 and 2006 were reviewed. Of these, 15,102 patients met the inclusion criteria; 121 patients developed acute renal failure (0.8%), and 14 required renal replacement therapy (0.1%). Seven independent preoperative predictors were identified (P < 0.05): age, emergent surgery, liver disease, body mass index, high-risk surgery, peripheral vascular occlusive disease, and chronic obstructive pulmonary disease necessitating chronic bronchodilator therapy. Several intraoperative management variables were independent predictors of acute renal failure: total vasopressor dose administered, use of a vasopressor infusion, and diuretic administration. Acute renal failure was associated with increased 30-day, 60-day, and 1-yr all-cause mortality.
Several preoperative predictors previously reported to be associated with acute renal failure after cardiac surgery were also found to be associated with acute renal failure after noncardiac surgery. The use of vasopressor and diuretics is also associated with acute renal failure.
Background
Survival for pancreatic ductal adenocarcinoma is low, the role of adjuvant therapy remains controversial, and recent data suggest adjuvant chemoradiation (CRT) may decrease survival ...compared with surgery alone. Our goal was to examine efficacy of adjuvant CRT in resected pancreatic adenocarcinoma compared with surgery alone.
Materials and Methods
Patients with pancreatic adenocarcinoma at Johns Hopkins Hospital (
n
= 794, 1993–2005) and Mayo Clinic (
n
= 478, 1985–2005) following resection who were observed (
n
= 509) or received adjuvant 5-FU based CRT (median dose 50.4 Gy;
n
= 583) were included. Cox survival and propensity score analyses assessed associations with overall survival. Matched-pair analysis by treatment group (1:1) based on institution, age, sex, tumor size/stage, differentiation, margin, and node positivity with
N
= 496 (
n
= 248 per treatment arm) was performed.
Results
Median survival was 18.8 months. Overall survival (OS) was longer among recipients of CRT versus surgery alone (median survival 21.1 vs. 15.5 months,
P
< .001; 2- and 5-year OS 44.7 vs. 34.6%; 22.3 vs. 16.1%,
P
< .001). Compared with surgery alone, adjuvant CRT improved survival in propensity score analysis for all patients by 33% (
P
< .001), with improved survival when stratified by age, margin, node, and T-stage (RR = 0.57–0.75,
P
< .05). Matched-pair analysis demonstrated OS was longer with CRT (21.9 vs. 14.3 months median survival; 2- and 5-year OS 45.5 vs. 31.4%; 25.4 vs. 12.2%,
P
< .001).
Conclusions
Adjuvant CRT is associated with improved survival after pancreaticoduodenectomy. Adjuvant CRT was not associated with decreased survival in any risk group, even in propensity score and matched-pair analyses. Further studies evaluating adjuvant chemotherapy compared with adjuvant chemoradiation are needed to determine the most effective combination of systemic and local–regional therapy to achieve optimal survival results.
To examine the efficacy of adjuvant chemoradiotherapy after pancreaticoduodenectomy (PD) for pancreatic adenocarcinoma (PC) in patients undergoing resection at Johns Hopkins Hospital (JHH; Baltimore, ...MD).
Between August 30, 1993, and February 28, 2005, a total of 908 patients underwent PD for PC at JHH. A prospective database was reviewed to determine which patients received fluorouracil (FU) -based CRT. Excluded patients had metastatic disease, died 60 or fewer days after PD, received preoperative therapy, an experimental vaccine, adjuvant chemotherapy or radiation alone. The final cohort includes 616 patients.
The median follow-up was 17.8 months (interquartile range, 9.7 to 33.5 months). Overall median survival was 17.9 months (95% CI, 16.3 to 19.5 months). Groups were similar with respect to tumor size, nodal status, and margin status, but the CRT group was younger (P < .001), and less likely to present with a severe comorbid disease (P = .001). Patients with carcinomas larger than 3 cm (P = .001), grade 3 and 4 (P < .001), margin-positive resection (P = .001), and complications after surgery (P = .017) had poor long-term survival. Patients receiving CRT experienced an improved median (21.2 v 14.4 months; P < .001), 2-year (43.9% v 31.9%), and 5-year (20.1% v 15.4%) survival compared with no CRT. After controlling for high-risk features, CRT was still associated with improved survival (relative risk = 0.74; 95% CI, 0.62 to 0.89).
These data suggest that adjuvant concurrent FU-based CRT significantly improves survival after PD for PC when compared with patients not receiving CRT. These data support the use of combined adjuvant CRT for PC.
The purpose of this study was to determine the incidence of nephrogenic systemic fibrosis and its relation to renal failure and the administration of gadolinium-based contrast material at an academic ...medical center.
A dermatopathology database was searched to identify patients in whom nephrogenic systemic fibrosis was diagnosed. The medical records of these patients were reviewed. Renal function concurrent with any administration of gadolinium-based contrast material was assessed, as was patient outcome. A database of patients undergoing long-term dialysis was reviewed separately to determine how many had received gadolinium and the frequency of nephrogenic systemic fibrosis among these patients.
Twenty-nine patients were found to have had nephrogenic systemic fibrosis between November 15, 1999, and December 31, 2006. It was known that gadolinium-based contrast material had been administered to 25 of these patients before diagnosis. All 29 patients had compromised renal function (27 had chronic renal failure, and two had acute renal failure). Determination of the temporal relation between gadolinium-based contrast administration and symptom onset often was difficult. Only eight patients had severe morbidity. Nephrogenic systemic fibrosis developed in 12 (2.9%) of 414 patients undergoing long-term dialysis who received gadolinium-based contrast material.
We confirm the strong association between nephrogenic systemic fibrosis and gadolinium-based contrast administration. Although the use of high doses of gadolinium and the occurrence of chronic renal failure have been implicated in other reports, several of our patients received standard doses of gadolinium, and two had transient acute renal failure before diagnosis. Most patients had mild or moderate symptoms. Nephrogenic systemic fibrosis developed in 2.9% of patients undergoing long-term dialysis who received gadolinium-based contrast material but in none of the long-term dialysis patients who did not receive gadolinium-based contrast material.
Decisions about dialysis for advanced kidney disease are often strongly shaped by sociocultural and system-level factors rather than the priorities and values of individual patients. We examined ...international variation in the uptake of conservative approaches to the care of patients with advanced kidney disease, in particular discontinuation of dialysis.
We employed an observational cohort study design using data collected from patients maintained on long-term hemodialysis between 1996 and 2015 in facilities across 12 developed countries participating in the Dialysis Outcomes and Practice Patterns Study (DOPPS). The main outcome was discontinuation of dialysis therapy. We analyzed the association between several patient characteristics and time to dialysis discontinuation by country and phase of study entry.
A total of 259 343 DOPPS patients contributed data to the study, of whom 48 519 (18.7%) died during the study period. Of the decedents, 5808 (12.0%) discontinued dialysis before death. Rates of discontinuation were higher within the first few months after initiation of dialysis, among older adults, among those with a greater number of comorbidities and among those living in an institution. After adjustment for age, sex, dialysis duration, diabetes and dialysis era, rates of discontinuation were highest in Canada, the United States and Australia/New Zealand (33.8, 31.4 and 21.5 per 1000/yr, respectively) and lowest in Japan and Italy (< 0.1 per 1000/yr). Crude discontinuation rates were highest in dialysis facilities that were more likely to offer comprehensive conservative renal care to older adults.
We found persistent international variation in average rates of dialysis discontinuation not explained by differences in patient case-mix. These differences may reflect physician-, facility- and society-level differences in clinical practice. There may be opportunities for international cross-collaboration to improve support for patients with end-stage renal disease who prefer a more conservative approach.
Nephrogenic fibrosing dermopathy is a newly recognized cutaneous fibrosing disorder marked by the acute onset of induration involving the upper and lower limbs in patients with acute or chronic renal ...failure. The etiology, pathogenesis, associated clinical conditions (other than renal failure), and ultimate course have not been defined in the few cases studied. Presently, there is no effective treatment, and the condition persists in most patients.
Clinical and histopathologic data on 13 patients from our institution with the diagnosis of nephrogenic fibrosing dermopathy were reviewed. Several clinical and laboratory parameters were examined to see if any were consistently associated with the disease. Biopsy specimens were analyzed to determine if there was a pattern to the evolution of fibrosis in these patients.
All 13 patients had renal failure before disease onset: 8 were undergoing chronic hemodialysis, 2 were undergoing chronic peritoneal dialysis, and 3 with acute renal failure had never undergone dialysis before the development of dermopathy. Most patients had other serious underlying medical conditions. Many patients were taking erythropoietin, cyclosporine, or both before the onset of disease. In transplant patients, no histocompatibility antigens were found to be associated with the disease. There were various laboratory abnormalities, but none were consistently associated with the condition. In skin biopsy specimens taken 7 to 180 days after disease onset, there were histopathologic changes suggestive of a tissue reaction to injury, as well as the development of smooth muscle actin–positive myofibroblasts.
Nephrogenic fibrosing dermopathy is a novel cutaneous fibrosing disorder that is distinguished from other sclerosing or fibrosing skin disorders by distinctive clinical and histopathologic findings occurring in the setting of renal failure. There were no additional clinical risk factors or laboratory findings common to the 13 patients studied, other than renal failure. The resemblance to a tissue injury reaction and the presence of myofibroblasts in the tissue specimens suggest that fibrogenic cytokines may be involved in the evolution of the disease.
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.
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