Duration Of Steroid Use Research Articles

Biologics Do Not Reduce the Long Term Risk of Surgery in Patients with IBD

Purpose: Almost 50% of patients with inflammatory bowel disease (IBD) will undergo surgery for their disease at some stage of its clinical course. Surgery in IBD is not usually followed by clinical remission and may result in various post operative complications. The purpose of this review is to characterize the factors that may have an influence on the risk of surgery in patients with IBD.Table: [1685]Methods: A retrospective chart review of 792 IBD patients was done of which 243 patients had surgery. All the factors that had an influence on the incidence of surgery were identified. Odds ratio (OR) and p value were calculated using the Fischer exact test for nominal data and T test for continuous data. Results: Out of the 792 patients 30.7% (n=243) had surgery, of which 86% (n=208, OR 7.65, p value <0.05) had CD, 14% (n=35) had UC. Of these patients 56% (n=137, OR 0.91, P value not significant) were females and 44% (n=106) were males. The average age among those who had surgery was 46±15 years (p value< 0.05), average duration of disease was 16±12.5years (p<0.05), average HBI/Lichtiger score was 7.7±6 (p value<0.05), cumulative duration of steroid use was 45±82 months (p<0.05), average Calprotectin was 373.5±591 mcg/g (p value not significant) and average BMI was 26±6 (p value not significant). The other factors that had significant effect on the increase in surgery rates were CRP>2 mg/dl 26% (n=63, OR 1.96, p<0.05), anemia 43% (n=104, OR 1.43, p<0.05) and use of biologic agent 49% (n=118, OR 3.2, p<0.05). Average duration of biologics in patient who underwent surgery was 26.7±28.5 months as compared to 16.4±25.8 months in those who have not had surgery yet. Conclusion: Factors that increased the risk of surgery rates in IBD patients were age, duration of disease, HBI/Lichtiger score, cumulative duration of steroid use, CRP>2, anemia and use of biologic agent. Biologic agents do not offer long term risk reduction of surgery.

The Impact of Early Corticosteroid Withdrawal on Graft Survival in Liver Transplant Recipients

BackgroundThere has been increased interest in recent years in reducing or eliminating steroids from the immunosuppression regimen of transplant recipients to reduce adverse effects associated with their use. The purpose of this study was to compare clinical outcomes between early versus late steroid withdrawal after liver transplant to determine the optimal duration of steroid use in this population. MethodsThis large-scale, retrospective analysis of liver transplants occurred at our institution between 2000 and 2009. Patients were excluded if they were <18 years old, received a multiorgan transplant, or remained on steroids for >1 year. The early steroid withdrawal group had steroids eliminated by 3 months posttransplant; late steroid withdrawal patients had steroids withdrawn between 3 and 12 months posttransplant. ResultsA total of 586 liver transplants occurred during the study period; 330 patients were included in the analysis. Graft survival was significantly lower in the early steroid withdrawal group. There was no difference in patient survival or overall acute rejection. However, the late steroid withdrawal group had a significantly higher rate of early acute rejection episodes. There was no difference with regard to new-onset diabetes after transplant, hyperlipidemia, or cardiovascular events between groups. ConclusionThe results of this study suggest that late corticosteroid withdrawal is associated with better long-term graft survival without increasing the rates of diabetes, hyperlipidemia, or cardiovascular events in liver transplant recipients. A prospective study is warranted to confirm these findings.

Steroid elimination within 24 hours after orthotopic liver transplantation: effectiveness and tolerability

Steroids have been the mainstay of immunosuppressive regimen in liver transplantation. However, the use of steroids is associated with various post-transplant complications. This study evaluated the efficacy and safety of reduced immunosuppressive regimen with steroids (steroid elimination within 24 hours post-transplant) in a cohort of Chinese liver transplant recipients. Seventy-six patients in line with the selection criteria were enrolled in this prospective study. All patients received anti-IL-2 receptor antibody induction and tacrolimus-based maintenance therapy. The recipients were divided into two groups according to the duration of steroid use: 40 transplant in a 3-month withdrawal group and the remaining 36 in a 24-hour elimination group. Recipient survival, post-operative infections, biopsy-proven acute rejection and steroid-resistant acute rejection, non-healing wound, recurrence of hepatitis B virus (HBV) and hepatocellular carcinoma (HCC), de novo diabetes, hyperlipidemia and hypertension were assessed in the two groups. There was no significant difference in patient survival, incidence of acute rejection episodes and hyperlipidemia, and recurrence of HBV and HCC between the two groups. However, the incidence rates of post-transplant infection, non-healing wound, de novo diabetes and hypertension were significantly lower in the 24-hour elimination group than in the 3-month withdrawal group (all P values <0.05). Under anti-IL-2 receptor antibody induction and tacrolimus-based maintainance, steroid elimination within 24 hours post-transplant is associated with reduced steroid-related complications without increasing the risk of rejection.

Clinical and Hematologic Manifestations in Patients with Diamond-Blackfan Anemia

Abstract 4378 BackgroundDiamond-Blackfan anemia (DBA), characterized by impaired red cell production, is a rare condition that usually occurs symptomatic in early infancy. The purpose of this study was to assess the nationwide experiences of DBA that were encountered over a period of 20 years as a part of further molecular analyses. MethodsMedical records of 56 patients diagnosed to have DBA were reviewed retrospectively from Nov. 1984 to July 31, 2010. Fifteen clinics including 13 university hospitals have been participated. ResultsMale to female ratio was 1.67:1 (males 35 cases, females 21). The median age of diagnosis was 4 months (range birth to 52 months of age), with the diagnosis of 74.1% before 1 year of age. From 2000 to 2009, 33 cases with DBA were registered, which showed the incidence of 6.6 cases per million. Excluding growth retardation, 21 cases (38.2%) showed congenital defects: thumb deformities (8 cases), ptosis (5), coarctation of aorta (5), ventricular septal defect (4), strabismus (3), cleft palate (2), mitral valve prolapsed (2). The mean hemoglobin (Hb) concentration was 5.1±1.9 g/dL, and median, 5.2 g/dL. The mean MCV was 93.4±11.6 fL, mean HbF 7.7±11.3%, mean reticulocytes 19,700/mm3 and mean adenosine deaminase 21.3. The mean cellularity of bone marrow was 75%, with the ME ratio of 20.4:1. Among 47 patients who had been treated with steroids, 23 patients (48.9%) did not need further steroids after remission. The mean duration of steroid use was 7 years and 2 months (maximum 22 years). Among 28 cases who received steroid, 9 patients had been controlled with the oral steroid of 5 mg or less per day. Eight patients with DBA that received hematopoietic transplantation have survived. Cancers developed in 2 cases (3.6%). ConclusionThe incidence of DBA is similar with the data already published, but male predilection in our study. Although all patients responded to initial treatment with steroids, about a half needed further steroids after remission. It is necessary to collect the further data including management pathways from nationwide DBA registries, with the molecular analyses. Disclosures:No relevant conflicts of interest to declare.

Prevalence and Risk of Avascular Osteonecrosis in Inflammatory Bowel Disease

Purpose: Avascular necrosis (AVN) of bone is a dreaded complication of prolonged steroid use. Case series in patients with inflammatory bowel disease (IBD) have reported an association between steroids and AVN of the hip/neck of femur and other sites. However, the prevalence of AVN has not been studied in depth in a large IBD population. Given that IBD patients often develop steroid-dependent disease, we sought to investigate the prevalence of AVN in IBD and to determine whether risk is related to length of steroid exposure. Methods: Using a large administrative health claims database, we conducted a retrospective cohort analysis to determine the prevalence AVN in IBD and identify factors associated with AVN occurrence. ICD-9 codes were used to identify subjects with IBD and diagnosis of AVN. We excluded subjects who also had diagnoses of lupus and other disorders for which steroids are used frequently. Treatment with steroids was documented and categorized into four exposure groups based on duration of use. All subjects were followed forward in time until the occurrence of AVN, end of capture period (Dec 2006) or end of enrollment. The prevalence of AVN in IBD was compared to that in a non-IBD population (1:5 ratio). Logistic regression was used to calculate independent risk (expressed as odds ratio [OR]) for AVN stratified by steroid exposure. Results: 53,434 IBD subjects were included and mean follow-up time was 2.4 years. The overall prevalence of AVN was 0.3% in IBD and 0.2% in non-IBD subjects. The rates were similar for Crohn's disease (CD) and ulcerative colitis (UC) but the steroid exposure overall was greater in CD. The risk of AVN with any steroid exposure compared to none was greater in CD (OR=2.1, P=0.0019) than in UC (OR=1.1, P=0.74). In a multivariate analysis, risk of AVN increased with longer steroid exposure, after adjustment for age and gender (Table). Conclusion: Among IBD patients, risk of AVN increases significantly with greater duration of steroid use. The prevalence is higher in CD than in UC but this difference may be due to lower steroid exposure in UC. There does not appear to be an increased risk for AVN due to IBD alone.Table

Pneumocystis jirovecii pneumonia in renal transplant recipients occurring after discontinuation of prophylaxis: a case–control study

A case–control study was conducted to identify risk factors for Pneumocystis jirovecii pneumonia (PCP) in renal transplant recipients. Eleven cases of PCP were matched with 22 controls. Cases occurred a median of 18 months after transplantation, and none of the recipients was receiving prophylaxis. Univariate analysis showed that graft rejection, duration of steroid use, use of mammalian target of rapamycin (mTOR) inhibitors and lymphocytopenia at the time of prophylaxis discontinuation were risk factors for PCP. In the multivariate model, only graft rejection (OR 8.66, p 0.017) remained significantly associated with PCP. In patients with a history of graft rejection, PCP prophylaxis should be maintained, especially among those with lymphocytopenia.

Describing Characteristics and Chronology of Ulcerative Colitis in African Americans

To describe patient and disease characteristics, treatment response and outcome in African Americans (AA) with ulcerative colitis (UC). Single-center, retrospective study. We reviewed records of 50 AA patients with an established diagnosis of UC seen at the outpatient clinic between 2000 and 2009. Demographic and clinical variables were examined using descriptive statistics. The mean age at diagnosis was 37 years (range of 12-69 years). At the end of observation, mean duration of disease was 11 years and mean patient age was 47 years. Men and women were equally represented. The mean body mass index (BMI) was 28 mg/kg2. Twenty nine (73%) patients were overweight or obese. At diagnosis, 24 (48%) patients had pancolitis, 15 (30%) had left sided disease and 11 (22%) had proctitis/proctosigmoiditis. Nineteen (38%) patients had extra-intestinal manifestations which were predominantly rheumatologic (84%). Eight (20%) and 4 (10%) patients had family history of inflammatory bowel disease (IBD) and colorectal cancer respectively. Twenty three (46%) patients had a past history of 5-ASA agent use and 34 (68%) were on a 5-ASA agent at last observation. The most common reason for discontinuation of a 5-ASA agent was lack of response. Mesalamine Delayed-Release was overall the most common5-ASA agent used and 16 (57%) of the patients using a 5-ASA agent were on it at last observation. The second most common 5-ASA agent being used was sulfasalazine. Twelve (24%) patients had a past history of azathioprine/6-mercaptopurine (AZA/6-MP) use whereas six (12%) were on AZA/6-MP at last observation. Four (8%) patients had a past history of biologic use that included adalimumabor infliximab. Five (10%) patients were on a biologic at last observation. The two most common reasons for discontinuation of both AZA/6-MP and biologics were lack of response and intolerance. Seventeen (34%) patients had a significant history of steroid use with the mean duration of steroid use per year of 60 days. Eight (16%) patients had undergone total colectomy with ileal J pouch-anal anastomosis. The mean duration to surgery in these patients was 8 years. Calculation of average clinical disease activity during last year of observation revealed that 23 (46%) patients were in clinical remission, 15 (30%) had mild disease whereas 12 (24%) had moderate to severe disease. The corresponding last outpatient endoscopic evaluation revealed that 16 (36%) patients' disease was inactive, 14(32%) had mild mucosal disease whereas 14 (32%) patients had moderate to severe mucosal disease. None of the patients were found to have dysplasia and none died. Our study generally agrees with findings of previous studies done on AA patients with UC. These include a relatively low rate of steroid, traditional immune modulator and biologic use as well as a low rate of surgical intervention, with the rate of 5-ASA agent use being high. Notable difference includes an older age at diagnosis of UC in our cohort. At a given time, approximately 75% AA patients with UC are either in clinical remission or have mild clinical disease and 66% have inactive or mild mucosal disease.

Pneumocystis jiroveciiPneumonia in Renal Transplant Recipients occurring after prophylaxis discontinuation: a case control-study.

A case-control study was conducted to identify risk factors for Pneumocystis jirovecii pneumonia (PCP) in renal transplant recipients. Eleven cases of PCP were matched with 22 controls. Cases occurred a median of 18 months after transplantation, and none of the recipients was receiving prophylaxis. Univariate analysis showed that graft rejection, duration of steroid use, use of mammalian target of rapamycin (mTOR) inhibitors and lymphocytopenia at the time of prophylaxis discontinuation were risk factors for PCP. In the multivariate model, only graft rejection (OR 8.66, p 0.017) remained significantly associated with PCP. In patients with a history of graft rejection, PCP prophylaxis should be maintained, especially among those with lymphocytopenia.

Aggressive steroid weaning after cardiac transplantation is possible without the additional risk of significant rejection

Chronic steroid use after cardiac transplantation (CTX) is accompanied by co-morbidities that are dependent on length of exposure. A retrospective review of all CTX without induction therapy from 1999-2004. After 2001, an aggressive strategy of steroid weaning was introduced. A total of 165 patients underwent CTX, 82 from 1999-2001 (group 1) and 83 from 2002-2004 (group 2). There were no significant differences in recipient or donor characteristics between group 1 and group 2. The baseline calcineurin was cyclosporine in 41% and 5% (p < 0.0001) and tacrolimus in 59% and 95% (p < 0.0001), respectively. The mean duration of steroid use was 1023 d in group 1 and 383 d in group 2 (p < 0.0001). The overall incidence of any > or =ISHLT grade 3A rejection per year after CTX for group 1 vs. group 2 was as follows: year 1: 40% vs. 49% (p = NS) and year 2: 7.4% vs. 9.2% (p = NS). Steroid withdrawal by one yr after CTX using a contemporary immunosuppressive regimen is possible in most patients. In comparison with a slower steroid wean, a faster wean is not associated with an excess of significant rejection in the first two yr post CTX.

Long-term Outcomes of Penetrating Keratoplasty in Chronic and Delayed Mustard Gas Keratitis

To report the long-term outcomes of penetrating keratoplasty (PKP) in war victims with chronic and delayed mustard gas keratitis. This noncomparative interventional case series includes patients with advanced chronic or delayed mustard gas keratitis who had undergone PKP from 1989 to 2006. Best-corrected visual acuity (BCVA), graft clarity, episodes of graft rejection, duration of steroid use, and complications were evaluated. Histopathologic features of excised corneal buttons were also evaluated. Overall, 22 eyes of 19 patients underwent PKP. Mean age at the time of surgery was 41 +/- 4.6 years (range, 36-54 years), and mean follow-up duration was 40.9 +/- 48 months (range, 4-204 months). The graft remained clear in 17 (77.3%) eyes and failed in 5 (22.7%) eyes. Overall, 13 (59.1%) eyes experienced episodes of endothelial rejection, and 5 (22.7%) eyes had subepithelial immune rejection, 4 of which had simultaneous endothelial rejection. Fifteen (68.2%) eyes received topical steroids for >6 months. Fourteen (63.6%) eyes developed cataracts, leading to cataract extraction in 7 eyes. One eye developed steroid-induced glaucoma after multiple episodes of endothelial graft rejections. Mean preoperative BCVA was 1.92 +/- 0.63 logMAR, which improved to 1.04 +/- 0.65 logMAR (20/200) overall and 0.8 +/- 0.3 logMAR (20/120) in eyes with clear grafts (P < 0.001). Main histopathologic features of excised corneal buttons included corneal thinning and ulceration, loss of keratocytes, acute and chronic inflammation, stromal vascularization, and degenerative sequelae of long-standing inflammation. PKP in chronic or delayed-onset mustard gas keratitis should be considered as a high-risk graft; however, with appropriate management, graft clarity and visual outcomes may be favorable.

Prospective, long-term evaluation of steroid-induced glaucoma

To evaluate the intraocular pressure (IOP) after cessation of steroid use in steroid-induced glaucoma and its control with medication or surgery. Thirty-four eyes of 34 patients having steroid-induced glaucoma were prospectively evaluated after cessation of steroid for IOP, visual acuity, and optic disc status at 3 months, and every 3 months for 18 months. Topical steroid use (73.5%) was the most frequent cause for glaucoma. The baseline IOP was 35.47+/-12.59 mmHg. The baseline vertical cup-disc ratio correlated with duration of steroid use (P=0.014) and the baseline IOP (P<0.0001). In 25 patients (73.5%), IOP could be controlled by topical medications alone, whereas nine patients (26.5%) required surgery. The mean baseline IOP in eyes requiring surgery was 49.67+/-13.28 mmHg and in eyes managed medically, 30.36+/-7.51 mmHg (P=0.002). The vertical cup-disc ratio in surgically treated patient was 0.87+/-0.13:1 as compared to 0.71+/-0.15:1 (P=0.012) in the medically treated group. At 6, 12, and 18 months follow-up, 22 (64.7%), 33 (97.1%), and all 34 (100%) patients were off treatment, respectively. Patients with steroid-induced glaucoma, who were <or=20 years old, with a higher IOP, and greater glaucomatous optic neuropathy, were more likely to need surgery. After cessation of steroid therapy, all eyes were off treatment at 18 months.

Dose and duration of dexamethasone in patients with high grade gliomas (HGG): Relationship to steroid myopathy (SM)

18517 Background: Steroids are critical in the management of HGG due to their ability to control peri-tumoral edema. Myopathy is a disabling complication of steroids leading to loss of ambulation and respiratory compromise. We sought to describe the use of steroids in the first 8 months after the diagnosis of HGG and its relationship to SM. Methods: Charts of all adults with HGG diagnosed and treated at Johns Hopkins Hospital from June 2004 to May 2005 were reviewed. Patients who died in less than 8 months were excluded. Starting steroid dose, subsequent documented doses, initial date and dates of change were recorded. Only charts with the phrase “steroid myopathy” were defined as SM positive. Results: Twenty-eight patients met all inclusion criteria. The mean age was 57.2 ± 8.7 years and 19 (67.8%) were males. All patients (100%) received steroids. Dexamethasone was used exclusively. Ninety-three percent of patients received &gt;16mg/day and 36% were on &gt;16mg/day for at least a month. The average daily dose was 15.3 ± 7.1 mg. Mean cumulative dose was 2.8 ± 1.8 grams. The median peak dose was 40mg/day (range 16–120mg/day). Median days on steroids was 224 days (range 5–224 days) from diagnosis and 67.8% of patients were on continuous steroids for 8 months. Eleven (39% [95% CI: 22%-59%]) of the 28 patients were defined as SM. Seven of the 11 (63.6%) SM patients required wheelchairs versus two (11.8%) without SM (p = 0.004). Days on steroid was significantly longer (p = 0.012) in the SM group (214 ± 32 days) versus the non-SM group (155 ± 81days). No strong evidence supported differences between groups in total dose, average daily dose, peak dose or days on high dose steroids. Conclusions: Patients with HGG are exposed to high doses of steroids for long periods. SM was noted in 39% of our patients and most required wheelchairs within 8 months of diagnosis. These figures are likely significant underestimates given the amount of steroids administered and the retrospective nature of this study. Our data confirm prior reports of an association between duration of steroid use and SM. The findings highlight the need to prevent SM using alternate dosing schedules and agents and to develop effective treatment interventions for SM. No significant financial relationships to disclose.

Steroid Complications in Patients with Acute Graft Versus Host Disease.

Background: High dose steroid treatment remains to be the first line therapy for acute graft versus host disease (aGVHD) after allogeneic hematopoietic stem cell transplantation (HSCT). Although effective in controlling aGVHD, high dose steroids can cause multiple serious complications which can result in increased morbidity and mortality.Purpose: Our aim was to determine the frequency of steroid induced complications and to analyze risk factors for steroid-myopathy in patients with AML who developed grade 2 aGVHD after allogeneic HSCT.Patients and Methods: Inclusion criteria were:1) AML/MDS patients who received allogeneic HSCT between 1/1996 and 12/20012) grade 2 aGVHD treated with at least 2mg/kg of methylprednisolone3) post transplantation overall survival at least 100 days.Steroid induced complications reviewed were: cataracts, headaches, mood swings, hypertension, gastritis, hyperglycemia, osteopenia, myopathy, avascular necrosis, edema, hypokalemia and infections. Pre- and post-transplantation characteristics analyzed as risk factors for steroid-myopathy were: age, gender, race, history of diabetes, body mass index, HLA types, steroid use after HSCT prior to grade 2 acute GVHD and duration of steroid use for acute GVHD. Logistic regression analysis was used for risk factor evaluation. Steroid-myopathy was defined as proximal muscle weakness, atrophy and myalgia in the absence of genetic, inflammatory or drug-induced etiologies other than steroid use.Results: 178 AML /MDS patients were transplanted during the study period. 70 patients (37 males and 33 females) with a median age of 43 (range, 21–66) were eligible for our study. Median duration of follow-up and median duration of steroid use after grade 2 aGVHD were 269 days and 127 days respectively. The number of patients and their frequency distribution of steroid induced complications were as follows: hyperglycemia, 43 (61.4%); hypertension, 35 (50%); cataracts, 10(14.3%); headaches, 7 (10%); mood swings,12(17.1%); gastritis, 7 (10%); myopathy, 32(45.7%); avascular necrosis, 1 (1.4%); edema, 22 (31.4%); hypokalemia, 52 (74.3%); bacterial infections, 55 (78.6%); viral infections, 39(55.7%); and fungal infections, 22(31.4%). For steroid-induced myopathy, male gender (RR=4.0, 95% CI=1.01–16.4, p=0.05), steroid use before acute GVHD grade II (RR=5.5, 95% CI=1.35–22.14, p=0.02) or steroid use more than 4 months after developing acute GVHD grade II (HR=6.4, 95% CI=1.38–29.94, p=0.02) were independent risk factors. 47 of 70 patients died with median overall survival of 10 months. 22 of 47 (46.8%) had steroid-myopathy and there was no increased mortality with steroid induced myopathy.Conclusion: Steroid therapy for aGVHD after allogeneic HSCT in AML/MDS patients is associated with frequent toxicities. The possibility of identifying prognostic factors for steroid toxicities support the study and development of strategies that may ameliorate or prevent steroid induced complications.

Oral Prednisolone Produces a Durable Response in Pediatric Myelodysplastic Syndromes (MDS).

Treatment options for children with MDS are limited except for allogeneic bone marrow transplantation. We present our experience with the use of long duration corticosteroids in children with MDS. Fifty five children (age< 15 years) with pediatric MDS or myelofibrosis treated between 1991–2004 with corticosteroids were analyzed. All of these patients presented with cytopenia involving one or more lineages and a hypercellular marrow with dysplasia and increased reticulin. Prednisolone was started at 1 mg/kg daily or on alternate days for a period of 1–2 months. If there was no response, steroids were rapidly tapered and stopped. In children who showed a response, the steroids were slowly tapered to alternate day steroids and stopped over a period of 6–12 months. In patients who had relapse of symptoms on tapering, the dose of steroids was increased to previous levels and then tapered at a much slower rate. The median age was 3 years (range: 3 months – 14 years) with 36 males and 19 females. Forty six has pediatric MDS while 10 had pediatric myelofibrosis. The median duration of symptoms prior to starting steroids was 7 months (range: 1–24). Forty one patients (74.5%) showed a response with 31 (56.4%) showing a complete response while 10 patients (18.1%) showed a partial response with improvement in counts and transfusion independence. Fourteen patients (25.5%) showed no improvement and continued to be transfusion dependant. Fourteen of the 41 patients (34%) who responded to steroids relapsed on tapering of steroids but showed response to repeat courses of steroids. The median duration of steroid use in patients who have responded is 12 months (range: 1 – 96). None of the patients had any serious side effects including infections, hypertension or diabetes except one patient who developed disseminated tuberculosis 12 months after stopping steroids. Nine patients have shown progression of disease while 1 patient developed features of SLE 24 months after diagnosis of MDS. At a median follow up of 34 months (range: 4– 120), 32 patients (58%) are alive with 27 (49%) in complete remission [14 off treatment, 13 on treatment] and 5 in partial remission but transfusion independent. Prednisolone induces a durable response in children with MDS. The biological basis of this response needs to be evaluated.

Posterior Fossa Metastases: Risk of Leptomeningeal Disease When Treated with Stereotactic Radiosurgery Compared to Surgery

Leptomeningeal disease (LMD) represents a diffuse form of central nervous system metastatic disease that is often associated with poor quality of life and prognosis. Our objective was to compare the incidence of LMD in patients with posterior fossa metastases (PFM) following stereotactic radiosurgery (SRS) versus surgical resection. The medical records of 93 patients aged 57.9 +/- 10.8 years (mean +/- SD) with PFM treated at the Cleveland Clinic from 1995 to 2001 were analyzed retrospectively. Treatments consisted of surgery with whole brain radiation therapy (WBRT) or SRS with or without WBRT. The impact of age, Karnofsky performance status (KPS) at presentation, Radiation Therapy Oncology Group, recursive partitioning analysis (RPA) class, status of extracranial disease, number, size, volume, pathology of brain metastases and steroid use were studied using univariate and multivariate analyses. There were 80 evaluable patients (10 lost to follow-up and three excluded for supratentorial surgery with subsequent LMD). LMD occurred after the surgical removal of the PFM in 9 of 18 patients (50%), whereas LMD occurred after SRS in 4 of 62 patients (6.5%) (p = 0.0028). Multivariate analysis also showed that patients who had surgery were more likely to develop LMD compared to patients treated with SRS (p = 0.0024). Patients had a median KPS decline of 30 points after LMD was diagnosed. There was no statistically significant difference in survival of patients with LMD and the rest of the patients (13.5 vs. 11.7 months, p = 0.7659). Patients treated surgically had significantly larger lesions (3.43 +/- 0.74 vs. 1.96 +/- 0.95 cm maximum diameter, p < 0.0001). All surgical patients belonged to RPA class II at diagnosis. Their survival was not different from the RPA class II patients in the SRS group. Surgery and SRS had comparable complication rates (8.1% vs. 5.6%, p = 0.99), although the surgical complications were more serious (e.g. hemorrhage, CSF leak). The duration of steroid use was longer after SRS compared to surgery (2.1 +/- 3.6 vs. 1.3 +/- 2.4 months); however, the difference was not statistically significant. Myopathy and psychosis in one patient after SRS, were the only steroid-related complications. There was no statistically significant association between the primary tumor type and the presence of LMD. In this retrospective analysis of patients with PFM, SRS was associated with a lower incidence of LMD than was surgery. Although LMD was associated with rapid and considerable decline in the quality of life, it did not influence the overall survival. SRS was associated with less serious complications than surgery. Surgery in this study was performed on patients with larger lesion sizes and a trend toward poorer initial performance status, which could bias these results. A prospective study directly comparing surgery and SRS and further evaluating the significance of LMD in PFM is warranted.

Patterns of disease and surgical treatment among United States veterans more than 50 years of age with ulcerative colitis

Background Ulcerative colitis (UC) is a clinical entity that predominantly affects young adults yet large series of middle age or elderly patients with UC are infrequently reported. The aim of this study is to identify patterns of disease, indications for operation, surgical treatment, and outcome of patients more than 50 years of age who required surgery for UC in Department of Veterans Affairs (DVA) Medical Centers. Methods A population-based study on all patients in 159 hospitals of the DVA from 1997 to 2001 was carried out. Data were compiled from several national computerized VA data sets. Supplementary information including demographic information, discharge summaries, operative reports and pathology reports were obtained from local medical records. Patient variables were entered into a computerized database and analyzed using the Pearson chi-square and Fisher's exact tests. Statistical significance is designated as P < 0.05. Results One hundred fifty-eight patients were evaluable. The mean age was 59 years (range 51–81); 99% were male. The mean duration of UC was 23 years (range 2 to 50). One hundred of the 158 patients had proctocolitis; 58 had either left-sided colitis or proctosigmoiditis. The mean dose of prednisone prior to surgery was 20 mg; the mean duration of steroid use was 8 years. The indications for elective surgery were intractability (59%), mass or stricture (27%), and dysplasia (14%). Twenty of the 158 patients (12%) were operated on emergently for either toxic colitis, perforation, or hemorrhage. One hundred three of the 158 underwent proctocolectomy and permanent ileostomy, 55 underwent a restorative proctocolectomy, and underwent a segmental colectomy. Twenty of the 158 patients were found to have dysplasia in their colectomy specimens; an additional 10 (7%) were found to have invasive cancer. Surgical morbidity was 22%. Overall mortality was 4% (7 of 158); all but 1 death occurred after emergent surgery. Mean hospitalization was 36 days (range 2 to 297). Conclusions Restorative proctocolectomy was performed in 36% of veterans more than 50 years of age requiring surgery for UC. The majority required surgery for intractable symptoms. Dysplasia and invasive cancer was found in 18% of patients. Mortality after surgery for acute surgical emergencies remains high.

A prospective survey of the use of dexamethasone on a palliative care unit.

One hundred and six consecutive patients started on glucocorticosteroids (steroids) according to a defined prescription policy were surveyed each week to document the indications for use, any beneficial effect, any toxicity incurred and the reason for stopping. All patients had advanced malignant disease and survived for a median of 40.5 days (range 1-398+ days) from the start of steroid treatment. Fifty-seven per cent of patients completed three or more assessments. The most common specific indications for starting steroids were spinal cord compression, cerebral metastases, lymphangitis carcinomatosa and intestinal obstruction. The most common non-specific indications were anorexia, nausea, low mood, pain and vomiting. The median duration of steroid use was 21.5 days (range 1-89 days). The most common reason for the discontinuation of steroids was death or deteriorating condition. Symptom scores improved at some stage for the majority of patients started on steroids for anorexia, nausea, pain, low mood, vomiting and weakness but not in patients complaining of dyspnoea or poor mobility. The most common side-effects that were most probably attributable to steroid therapy were oral candidosis and proximal myopathy. The benefits of steroids when used according to defined guidelines were thought to outweigh toxicity.

Preventing glucocorticoid-induced osteoporosis.

Glucocorticoids are a potent cause of osteoporosis and thus a potential source of substantial morbidity in patients who are already significantly disabled by their underlying condition. These agents interact with calcium metabolism at many levels; in particular they reduce the osteoblast's synthesis of the principal proteins of bone matrix. They also reduce circulating sex hormone concentrations, particularly in men and postmenopausal women. Glucocorticoids cause rapid bone loss within weeks of their introduction, but this loss continues even after many years of chronic use. About one third of patients will develop fractures, those with low initial bone densities (e.g., postmenopausal women) being at higher risk. Fracture risk can be assessed from a patient's age, body weight, duration of steroid use, average dose of glucocorticoid, past history of fracture and bone density. In those at high risk of fracture, bone density can be increased by use of sex hormone replacement (in men or women who have a demonstrable deficiency) or a bisphosphonate (e.g., etidronate, alendronate, risedronate). Calcitriol, calcitonin and fluoride may have roles as adjunctive therapies but documentation of their efficacy is less satisfactory. It is incumbent on all physicians supervising long-term glucocorticoid therapy to ensure that a skeletal assessment is carried out and that osteoporosis prophylaxis is instituted, where appropriate.

A multicenter trial of 6-mercaptopurine and prednisone in children with newly diagnosed Crohn's disease

Clinical experience suggests that 6-mercaptopurine (6-MP) is effective therapy for children with active steroid-dependent Crohn's disease (CD). We report the results of a prospective, placebo-controlled, multicenter trial evaluating the combination of 6-MP and prednisone as therapy for children with newly diagnosed moderate-to-severe CD. Fifty-five children (age, 13+/-2 years) were randomized to treatment with 6-MP (1.5 mg x kg(-1) x day(-1)) or placebo within 8 weeks of initial diagnosis. Both groups also received prednisone (40 mg/day). Prednisone dosage adjustments were based on a defined schedule determined by the change in a subject's disease activity score, and steroid administration was discontinued as remission was achieved. Study treatment with 6-MP or placebo continued for 18 months. Groups were comparable for age, sex, and site and activity of disease. In the 6-MP group, the duration of steroid use was shorter (P<0.001) and the cumulative steroid dose lower at 6, 12, and 18 months (P<0.01). Although remission was induced in 89% of both groups, only 9% of the remitters in the 6-MP group relapsed compared with 47% of controls (P = 0.007). Growth was comparable in both groups. No clinically significant adverse events occurred, although mild leukopenia and increases in aminotransferase activity were noted in the 6-MP group. Addition of 6-MP to a regimen of corticosteroids significantly lessens the need for prednisone and improves maintenance of remission. 6-MP should be part of the initial treatment regimen for children with newly diagnosed moderate-to-severe CD.

The effects of prebiopsy corticosteroid treatment on the diagnosis of mediastinal lymphoma

Background/Purpose: For children with probable mediastinal lymphoma and a high risk of cardiorespiratory morbidity, many centers recommend delaying the diagnostic biopsy for 24 to 48 hours while corticosteroids are administered to reduce tumor size and morbidity. This study was undertaken to determine the effect of preoperative steroid use on the accuracy of the pathological diagnosis and incidence of perioperative cardiorespiratory morbidity. Methods: From 1988 to 1998, 86 children were treated for mediastinal lymphoma. Twenty-three received steroid before biopsy (study group) because of clinical evidence of respiratory compromise, and the remaining 63 served as controls. Clinical parameters, steroid use, and detailed pathological findings obtained at initial and subsequent biopsies were reviewed. Steroid treatment was considered to have had an adverse effect on the pathological diagnosis if (1) a definitive diagnosis was delayed more that 1 month, (2) a definitive diagnosis could not be made, or (3) the extent of disease could not be staged with certainty. Results: Steroid treatment had an adverse effect on the pathological diagnosis in 5 of 23 (22%) children: 1 diagnostic delay, 3 failures of a definitive diagnosis, and 1 possible failure of staging. A definitive diagnosis was made in all control patients. Perioperative survival was 100% in both groups. At biopsy, only 3 children in the steroid treatment group and 2 children in the control group had moderate, nonfatal cardiorespiratory instability. Parameters of steroid use among children who had inaccurate pathological diagnoses or cardiorespiratory morbidity were not significantly different from those who did not. Conclusions: Steroid treatment before biopsy of mediastinal lymphoma may adversely affect the pathological accuracy or cause a delay in definitive diagnosis in a minority of cases. The dose and duration of steroid use was not related to outcome. Prebiopsy steroid appears to minimize the likelihood of cardiorespiratory morbidity in high-risk patients. J Pediatr Surg 35:973-976. Copyright © 2000 by W.B. Saunders Company.