The primary dose-limiting toxicity of stereotactic radiosurgery (SRS) is radiation necrosis (RN), which occurs after approximately 5% to 10% of treatments. This adverse event may worsen neurologic ...deficits, increase the frequency and cost of imaging, and necessitate prolonged treatment with steroids or antiangiogenic agents. Previous investigations have primarily identified lesion size and dosimetric constraints as risk factors for RN in small populations. We hypothesized that disease histology, receptor status, and mutational status are associated with RN.
All patients presenting with brain metastasis between 1997 and 2015 who underwent SRS and subsequent radiographic follow-up at a single tertiary-care institution were eligible for inclusion. The primary outcome was the cumulative incidence of radiographic RN. Multivariate competing risks regression was used to identify biological risk factors for RN.
1939 patients (5747 lesions) were eligible for inclusion; 285 patients (15%) experienced radiographic RN after the treatment of 427 (7%) lesions. After SRS, the median time to RN was 7.6 months. After multivariate analysis, graded prognostic assessment, renal pathology, lesion diameter, and the heterogeneity index remained independently predictive of RN in the pooled cohort. In subset analyses of individual pathologies, HER2-amplified status (hazard ratio HR 2.05, P=.02), BRAF V600+ mutational status (HR 0.33, P=.04), lung adenocarcinoma histology (HR 1.89, P=.04), and ALK rearrangement (HR 6.36, P<.01) were also associated with RN.
In the present investigation constituting the largest series of RN, several novel risk factors were identified, including renal histology, lung adenocarcinoma histology, HER2 amplification, and ALK/BRAF mutational status. These risk factors may be used to guide clinical trial design incorporating biological risk stratification or dose escalation. Future studies determining the optimal timing of targeted therapies are warranted to further define the risk of RN.
The incidence of radiation necrosis has increased secondary to greater use of combined modality therapy for brain tumors and stereotactic radiosurgery. Given that its characteristics on standard ...imaging are no different that tumor recurrence, it is difficult to diagnose without use of more sophisticated imaging and nuclear medicine scans, although the accuracy of such scans is controversial. Historically, treatment had been limited to steroids, hyperbaric oxygen, anticoagulants, and surgical resection. A recent prospective randomized study has confirmed the efficacy of bevacizumab in treating radiation necrosis. Novel therapies include using focused interstitial laser thermal therapy. This article will review the diagnosis and treatment of radiation necrosis.
Free T4 immunoassays are flawed during pregnancy Lee, Richard H., MD; Spencer, Carole A., PhD; Mestman, Jorge H., MD ...
American journal of obstetrics and gynecology,
03/2009, Letnik:
200, Številka:
3
Journal Article
Recenzirano
Objective The purpose of this study was to evaluate the diagnostic accuracies of 2 free thyroxine immunoassays during pregnancy. Study Design Serum was collected from healthy, thyroid peroxidase ...antibody-negative women during each trimester and nonpregnant controls. Thyrotropin, total T4 (TT4), free T4 index (FT4I), and 2 different FT4 immunoassays were studied. Results As expected, TT4 was elevated in all 3 trimesters compared to controls ( P < .001). FT4I was elevated in the 1st trimester as compared with controls ( P < .05) and returned to the nonpregnant range in the 2nd and 3rd trimesters. In contrast, 1st trimester FT4 immunoassay values were either comparable or lower than controls and by the 2nd and 3rd trimesters had decreased to approximately 65% of controls. Conclusion Neither FT4 immunoassay accurately reflects established free T4 changes during pregnancy. TT4 and the FT4I retained an appropriate inverse relationship with TSH throughout pregnancy and appear to provide a more reliable free T4 estimate.
To analyze the effect of dose escalation on treatment outcome in patients undergoing stereotactic radiosurgery (SRS) for trigeminal neuralgia (TN).
A retrospective review was performed of 870 ...patients who underwent SRS for a diagnosis of TN from 2 institutions. Patients were typically treated using a single 4-mm isocenter placed at the trigeminal nerve dorsal root entry zone. Patients were divided into groups based on treatment doses: ≤82 Gy (352 patients), 83 to 86 Gy (85 patients), and ≥90 Gy (433 patients). Pain response was classified using a categorical scoring system, with fair or poor pain control representing treatment failure. Treatment-related facial numbness was classified using the Barrow Neurological Institute scale. Log-rank tests were performed to test differences in time to pain failure or development of facial numbness for patients treated with different doses.
Median age at first pain onset was 63 years, median age at time of SRS was 71 years, and median follow-up was 36.5 months from the time of SRS. A majority of patients (827, 95%) were clinically diagnosed with typical TN. The 4-year rate of excellent to good pain relief was 87% (95% confidence interval 84%-90%). The 4-year rate of pain response was 79%, 82%, and 92% in patients treated to ≤82 Gy, 83 to 86 Gy, and ≥90 Gy, respectively. Patients treated to doses ≤82 Gy had an increased risk of pain failure after SRS, compared with patients treated to ≥90 Gy (hazard ratio 2.0, P=.0007). Rates of treatment-related facial numbness were similar among patients treated to doses ≥83 Gy. Nine patients (1%) were diagnosed with anesthesia dolorosa.
Dose escalation for TN to doses >82 Gy is associated with an improvement in response to treatment and duration of pain relief. Patients treated at these doses, however, should be counseled about the increased risk of treatment-related facial numbness.
To characterize quality-of-life (QOL) outcomes after stereotactic radiosurgery (SRS) for trigeminal neuralgia (TN).
The EuroQOL 5 Dimensions (EQ-5D) and Patient Health Questionnaire 9 (PHQ-9) were ...prospectively collected before and after SRS for 50 patients with TN. Pain response and treatment-related facial numbness were classified by Barrow Neurological Institute (BNI) scales. Differences in pooled QOL outcomes were tested with paired t tests and sign tests. The Kaplan-Meier method was used to estimate time-dependent improvements in the EQ-5D index, EQ-5D perceived health status (PHS), PHQ-9 score, and freedom from pain failure (BNI class IV-V) or facial numbness (BNI class III-IV).
Following SRS, the 12-month rate of freedom from pain failure was 92% (95% confidence interval CI, 77%-97%) while the 12-month rate of freedom from facial numbness was 89% (95% CI, 66%-97%). Significant improvements in the EQ-5D index (P<.01), PHS (P=.01), and PHQ-9 (P=.03) were observed, driven by the EQ-5D subscores for self-care and for pain and/or discomfort (P=.02 and P<.01, respectively). At 12 months after SRS, the actuarial rates of improvement in the EQ-5D, PHS, and PHQ-9 were 55% (95% CI, 40%-70%), 59% (95% CI, 40%-76%), and 59% (95% CI, 39%-76%), respectively. The median time to improvement in each of the QOL measures was 9 months (95% CI, 3-36 months) for the EQ-5D index, 5 months (95% CI, 3-36 months) for PHS, and 9 months (95% CI, 3-18 months) for the PHQ-9. On multivariate analysis, only higher prescription dose (86 Gy vs ≤82 Gy) was associated with improvement in the EQ-5D index (hazard ratio, 5.73; 95% CI, 1.85-22.33; P<.01).
Patients with TN treated with SRS reported significant improvements in multiple QOL measures, with the therapeutic benefit strongly driven by improvements in pain and/or discomfort and in self-care, along with lower rates of depression. In this analysis, there appears to be a correlation between prescription dose and treatment response as measured by the EQ-5D.
Abstract Background Patients with single brain metastasis (SBM) have better outcomes after stereotactic radiosurgery (SRS). We analyzed our SRS database to evaluate possible prognostic factors in ...patients with SBM. Methods 584 patients with SBM that were treated with SRS at our institution (2000-2012). Study endpoints were overall survival (OS), and distant and local intracranial progression free survival (DPFS and LPFS, respectively). Multivariable analysis was performed to develop prognostic models. Results Median OS was 10.8 months. 196 patients (36.7%) had distant progression and 102 patients (19.2%) had local progression. New SBM prognostic index (SPI) were devised for OS, DPFS, and LPFS. Graded Prognostic Assessment (GPA), neurological symptoms (P=0.01) and tumor volume (P =0.02) were independently associated with OS. The SPI for OS was defined: “unfavorable” (OS 7.3 months), “intermediate” (OS 10.6 months), and “favorable” (OS 19.8 months). For DPFS, age (P=.0029), tumor volume (P=0.0002), and prior WBRT (P= 0.027) were prognostic, and were used to define SPI for DPFS: “favorable” (6-month CIF = 10.9%), “intermediate” (6-month CIF = 16.7%) and “unfavorable” (6 month CIF 26.0%) (P <0.001). For LPFS, GPA (P=0.0012) and tumor volume (P=0.0004) were significant, and defined two groups in the LPFS SPI: “unfavorable” (6-month CIF = 12.3%) and “favorable” (6-month CIF =6%) (P <0.001). Conclusion This is the largest series of patients with SBM treated with SRS analyzed for OS, LPFS, and DPFS. SPI was devised for endpoints. Tumor volume had a significant association with all three endpoints. Neurologic symptoms, age, prior WBRT were also found to be prognostic.
Objective The management of infected aortic endografts is a challenging endeavor. Treatment of this problem has not been well defined as it is fairly uncommon. However, the incidence is increasing. ...This study examines the results of treatment at a single center for this morbid process. Methods A retrospective review was performed of patients treated for infected abdominal or thoracic endograft infection following previous abdominal or thoracic endovascular aneurysm repair. Data was reviewed for patient demographics, details of initial endograft implantation, presentation and timeline of subsequent infection, management of infected grafts, and outcomes during follow-up. Results Overall, 18 patients were treated for infected endografts (thoracic: six, abdominal:12). Three patients were treated between 2000 and 2006, corresponding to a 0.6% institutional incidence of endograft infection (3/473). There were no transfers for infected endografts from outside institutions. From 2006 to 2011, 15 patients underwent treatment. Six were institutional cases of infections (6/945, 0.6% infection rate), however, there was an increase in transfers (n = 9). Median time to presentation with infection from endograft implant was 90 days, with over one-half (61%) presenting within the first 3 months. Tissue and/or blood cultures were positive in 12/16 growing Escherichia coli (n = 1), group A streptococcus (n = 3), methicillin-resistant Staphylococcus aureus (n = 3), or polymicrobial infections (n = 7). The other four patients were culture negative with computed tomography evidence of gas surrounding the endograft and clinical sepsis. Ten patients (abdominal: eight, thoracic: two) were treated with endograft explantation. The remaining eight patients were considered too high-risk for explant or refused open surgery and were therefore managed conservatively without explant (abdominal: four, thoracic: four). At a mean follow-up of 24.7 months, aneurysm-related mortality was 38.9% (n = 7) and was higher for patients presenting with aortoenteric or aortobronchial fistulas (n = 6/10, 60%) ( P = .04) and for thoracic stent infections (n = 5/6; 83%) ( P = .03). The only survivor of a thoracic infection was managed surgically. Overall survival for patients with abdominal endografts (n = 12) was similar between the eight patients managed surgically (n = 6/8; 75%) and the four selected for medical management (n = 4/4; 100%) ( P = .39). All survivors remain on long-term suppressive antibiotics. Two additional patients died of unrelated causes during follow-up. Conclusions Endograft infection is a rare but increasing complication after abdominal or thoracic endovascular aneurysm repair, which carries significant associated morbidity and mortality. Most endograft infections occurred in proximity to other types of infection, suggesting that bacterial seeding of the endograft was the source. Aortoenteric and aortobronchial fistulas are common presentations, which portend a significantly worse prognosis. Thoracic endograft infections, which have the highest rate of fistulization, have the worst outcomes. Surgical excision continues to be standard of care but conservative management with intravenous antibiotics may be of benefit in certain patients with abdominal endograft infections.
Background: Endovascular repair for complex thoracic aortic pathology has emerged over the past decade as an alternative to open surgical repair. Reports suggest lower morbidity and mortality rates ...associated with endovascular interventions. The purpose of this report was to analyze a large single institution experience in endovascular thoracic aortic repair based on clinical presentation as well as within and outside specific instructions for use. Methods: Records of all patients undergoing thoracic aortic endografting at our institution were retrospectively reviewed for demographics, interventional indications and acuity, operative details, and clinical outcomes. Study outcomes were analyzed by clinical presentation (urgent/emergent vs elective) and aneurysm morphology that was within and outside specific instructions for use as recommended by the manufacturer. Results: Between March 2006 and October 2009, 96 patients underwent thoracic endografting for aneurysm (n = 43), transection (n = 7), penetrating ulcer (n = 11), dissection (n = 19; acute = 9, chronic = 10), pseudoaneurysm (n = 11), or miscellaneous indications (n = 5). Endografting was performed with various endografts (Gore TAG: 59; Medtrontic Talent: 26; Zenith-TX2: 7; Combination: 4.Involvement of the arch (n = 42, 43.75%) was treated with subclavian artery coverage without revascularization in 13 (13.5%), debranching in 20 (20.8%), and fenestration/stenting in 9 (9.38%). Involvement of the visceral vessels (n = 24, 25%) was treated with debranching in 15 (15.6%) or fenestration/stenting in 9 (9.4%). Patients had a mean follow-up of 11.5 ± 10.96 (range: 0-38) months. Overall mortality was 6.25% (n = 6). Mean intensive care unit stay was 6.26 ± 8.55 (range: 1-63, median: 4) days, and hospital stay was 9.97 ± 10.31 (range: 1-65, median: 65) days. Major complications were infrequent and included: spinal cord ischemia (n = 6, 6.25%), stroke (n = 6, 6.25%), myocardial infarction (n = 3, 3.15%), renal failure (n = 6, 6.25%), and wound complications (n = 9, 9.38%). Reoperation was required in 13 (13.54%), with early intervention in 2 (2.1%). The vast majority of patients were discharged directly to home (n = 66, 68.8%). There were no significant differences between death (1/49 2% vs 5/47 10.6%, P = .07), stroke (3/49 6% vs 3/47 6%, P = 1.0), or spinal cord ischemia (3/49 6% vs 3/47 6%, P = 1.0) when comparing urgent/emergent presentation to elective cases, respectively. However, there were significant differences in death (6/58 10.5% vs 0/38 0%, P = .04) and spinal cord ischemia (6/58 10.5% vs 0/38 0%, P = .04) but not stroke (5/58 8.8% vs 1/38 2.5%, P = .24 when procedures were performed outside the specific instructions for use. Conclusions: Results of this single-institution report suggest that endovascular thoracic aortic repair is a safe and effective treatment option for a variety of thoracic pathology including both elective and emergent cases. However, off-label usage of the devices is associated with a significantly higher risk of mortality and spinal cord ischemia, but the risk still appears acceptable given the majority of cases were emergent.
Background Management using femoral-popliteal vein (FPV) of aortic graft infections, failing aortofemoral bypass, and aortoiliac occlusive disease in young patients with a small aorta is now an ...accepted therapeutic method and is performed frequently at our institution. A high reintervention rate for FPV graft stenosis has recently been reported. The purpose of this study was to determine the incidence of FPV graft failure due to stenosis after neoaortoiliac system (NAIS) reconstruction, and to identify risk factors for this complication. Methods A review was performed of 240 patients who underwent NAIS reconstruction at our institution between January 1991 and December 2005. All patients were entered into a prospective database and were evaluated for the incidence of vein graft stenosis requiring reintervention, risk factors for stenosis, and the rate and type of reintervention required to assist patency. Patients with occlusion are evaluated and reported, but excluded from detailed analysis. Risk factors assessed included gender, operative features, FPV size (diameter), smoking history, and medical comorbidities. Results Of the 240 NAIS procedures performed during this time period, 11 (4.6%) patients have required 12 graft revisions (one patient required a second intervention) for stenosis using open and endovascular techniques. Over the same time period, graft occlusion occurred in nine patients (3.8%). This provided a primary patency at 2 and 5 years of 87% and 82%, and an assisted primary patency rate of 96% and 94%. Mean time to revision was 23.5 months (range 5.5 to 83.5 months). Median FPV graft size in the nonrevised patients was 7.8 mm (range 4.0 to 11.4 mm), and 6.4 mm (range 4.7 to 8.7 mm) in the revised group ( P = .006). Survival analysis revealed small vein graft size (<7.2 mm), coronary artery disease (CAD), and extensive smoking history as independent predictors of time to stenosis ( P = .002, .02, .01, respectively), with multivariable analysis confirming these results ( P = .002, .06, .012). Patients with CAD combined with small graft size were found to be at especially high risk for stenosis, with 8/36 (22.2%) requiring revision vs 3/184 (1.6%) of patients without both factors ( P < .0001). Conclusions FPV graft stenosis requiring revision after NAIS reconstruction is uncommon. Risk factors for stenosis include small graft size, history of CAD, and smoking. All patients merit aggressive counseling for smoking cessation, and patients exhibiting multiple risk factors should undergo close postoperative surveillance for graft stenosis.
Abstract Background It is generally difficult to place an iliac vein stent precisely at the iliocaval junction with venographic control or even with intravascular ultrasound guidance. Furthermore, ...mechanical properties of the Wallstent (Boston Scientific, Marlborough, Mass) can predispose precisely placed stents to distal displacement or stent collapse. Our center has thus advocated extending Wallstents 3 to 5 cm into the inferior vena cava to prevent complications of missed proximal lesions or stent migration. This technique has gradually been accepted, and concerns of jailing of contralateral flow were not initially recognized. We analyzed deep venous thrombosis (DVT) incidence following iliocaval stenting with two alternative techniques: (1) Wallstents with 3- to 5-cm extension into the inferior vena cava; and (2) a modified Z-stent (Cook Medical, Bloomington, Ind) technique, in which overlapping Wallstents end at the iliac confluence and caval extension is performed with a Z-stent placed at the top of the stack. The function of the Z-stent is to provide improved radial force at the iliocaval confluence and to prevent jailing of contralateral flow with larger stent interstices. Methods There were 755 limbs with consecutive Wallstent caval extensions (2006-2010) and 982 limbs with Z-stent extensions (2011-2015) analyzed for DVT incidence postoperatively. Results Demographics were similar for both groups. Mean age was 56 and 58 years in the Wallstent and Z-stent groups, respectively. There was a female predominance (Wallstent, 69%; Z-stent, 67%) and a higher incidence of left-sided disease (Wallstent, 66%; Z-stent, 56%) in both groups. There was a slightly higher incidence of post-thrombotic disease in the Z-stent subgroup (Wallstent, 53%; Z-stent, 68%). Cumulative freedom from contralateral DVT was 99% and 90% in the Z-stent and Wallstent groups, respectively ( P < .001) during the 5 years following stent placement. However, all three patients with DVT contralateral to a Z-stent actually had high placement of the Wallstent across the confluence. Thus, no patients with proper Z-stent technique had a contralateral DVT. Cumulative freedom from ipsilateral DVT was 97% and 82% in the Z-stent and Wallstent groups, respectively ( P < .001) during the 5 years following stent placement. The decrease in incidence of ipsilateral DVT appeared to be attributable to decreased missed distal lesions with increased operator experience and not attributable to the Z-stent itself. Conclusions Contralateral DVT incidence was significantly lower with the Z-stent modification. In addition, the Z-stent modification provides greater radial strength at the iliac-caval confluence and simplifies simultaneous or sequential bilateral stenting. Use of proper technique and intravascular ultrasound is essential to limit the incidence of ipsilateral DVT.
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