How Are Indeterminate Pulmonary Nodules at Diagnosis Associated with Survival in Patients with High-Grade Osteosarcoma?

BackgroundPulmonary metastases are a poor prognostic factor in patients with osteosarcoma; however, the clinical significance of subcentimeter lung nodules and whether they represent a tumor is not fully known. Because the clinician is faced with decisions regarding biopsy, resection, or observation of lung nodules and the potential impact they have on decisions about resection of the primary tumor, this remains an area of uncertainty in patient treatment. Surgical management of the primary tumor is tailored to prognosis, and it is unclear how aggressively patients with indeterminate pulmonary nodules (IPNs), defined as nodules smaller than 1 cm at presentation, should be treated. There is a clear need to better understand the clinical importance of these nodules.Questions/purposes(1) What percentage of patients with high-grade osteosarcoma and spindle cell sarcoma of bone have IPNs at diagnosis? (2) Are IPNs at diagnosis associated with worse metastasis-free and overall survival? (3) Are there any clinical or radiologic factors associated with worse overall survival in patients with IPN?MethodsBetween 2008 and 2016, 484 patients with a first presentation of osteosarcoma or spindle cell sarcoma of bone were retrospectively identified from an institutional database. Patients with the following were excluded: treatment at another institution (6%, 27 of 484), death related to complications of neoadjuvant chemotherapy (1%, 3 of 484), Grade 1 or 2 on final pathology (4%, 21 of 484) and lack of staging chest CT available for review (0.4%, 2 of 484). All patients with abnormalities on their staging chest CT underwent imaging re-review by a senior radiology consultant and were divided into three groups for comparison: no metastases (70%, 302 of 431), IPN (16%, 68 of 431), and metastases (14%, 61 of 431) at the time of diagnosis. A random subset of CT scans was reviewed by a senior radiology registrar and there was very good agreement between the two reviewers (κ = 0.88). Demographic and oncologic variables as well as treatment details and clinical course were gleaned from a longitudinally maintained institutional database. The three groups did not differ with regard to age, gender, subtype, presence of pathological fracture, tumor site, or chemotherapy-induced necrosis. They differed according to local control strategy and tumor size, with a larger proportion of patients in the metastases group presenting with larger tumor size and undergoing nonoperative treatment. There was no differential loss to follow-up among the three groups. Two percent (6 of 302) of patients with no metastases, no patients with IPN, and 2% (1 of 61) of patients with metastases were lost to follow-up at 1 year postdiagnosis but were not known to have died. Individual treatment decisions were determined as part of a multidisciplinary conference, but in general, patients without obvious metastases received (neo)adjuvant chemotherapy and surgical resection for local control. Patients in the no metastases and IPN groups did not differ in local control strategy. For patients in the IPN group, staging CT images were inspected for IPN characteristics including number, distribution, size, location, presence of mineralization, and shape. Subsequent chest CT images were examined by the same radiologist to reevaluate known nodules for interval change in size and to identify the presence of new nodules. A random subset of chest CT scans were re-reviewed by a senior radiology resident (κ = 0.62). The association of demographic and oncologic variables with metastasis-free and overall survival was first explored using the Kaplan-Meier method (log-rank test) in univariable analyses. All variables that were statistically significant (p < 0.05) in univariable analyses were entered into Cox regression multivariable analyses.ResultsFollowing re-review of staging chest CTs, IPNs were found in 16% (68 of 431) of patients, while an additional 14% (61 of 431) of patients had lung metastases (parenchymal nodules 10 mm or larger). After controlling for potential confounding variables like local control strategy, tumor size, and chemotherapy-induced necrosis, we found that the presence of an IPN was associated with worse overall survival and a higher incidence of metastases (hazard ratio 1.9 [95% CI 1.3 to 2.8]; p = 0.001 and HR 3.6 [95% CI 2.5 to 5.2]; p < 0.001, respectively). Two-year overall survival for patients with no metastases, IPN, or metastases was 83% [95% CI 78 to 87], 65% [95% CI 52 to 75] and 45% [95% CI 32 to 57], respectively (p = 0.001). In 74% (50 of 68) of patients with IPNs, it became apparent that they were true metastatic lesions at a median of 5.3 months. Eighty-six percent (43 of 50) of these patients had disease progression by 2 years after diagnosis. In multivariable analysis, local control strategy and tumor subtype correlated with overall survival for patients with IPNs. Patients who were treated nonoperatively and who had a secondary sarcoma had worse outcomes (HR 3.6 [95% CI 1.5 to 8.3]; p = 0.003 and HR 3.4 [95% CI 1.1 to 10.0]; p = 0.03). The presence of nodule mineralization was associated with improved overall survival in the univariable analysis (87% [95% CI 39 to 98] versus 57% [95% CI 43 to 69]; p = 0.008), however, because we could not control for other factors in a multivariable analysis, the relationship between mineralization and survival could not be determined. We were unable to detect an association between any other nodule radiologic features and survival.ConclusionThe findings show that the presence of IPNs at diagnosis is associated with poorer survival of affected patients compared with those with normal staging chest CTs. IPNs noted at presentation in patients with high-grade osteosarcoma and spindle cell sarcoma of bone should be discussed with the patient and be considered when making treatment decisions. Further work is required to elucidate how the nodules should be managed.Level of EvidenceLevel III, prognostic study.     

Postoperative radiation therapy in the management of lung cancer

Postoperative radiation therapy for lung cancer is still controversial. In a 9-year period, 69 patients with non-oat-cell carcinoma of the lung (16% stage I, 26% stage II, and 58% stage III) received such therapy. The radiation dose was less than 5,000 cGy in 42 patients, 5,000-5,900 cGy in 16, and 6,000 cGy or more in 11; follow-up ranged from 24 to 64 months. Actuarial survival at 2 and 4 years was 50% and 16%, respectively, for squamous cell carcinoma, and 40% and 26% for adenocarcinoma. The 5-year survival for stages I, II, and III cancer was 29%, 17%, and 19%, respectively. Histologic findings and type of surgery did not affect survival, but the radiation dose apparently did. The 3-year survival for patients who received less than 6,000 cGy was 35%, compared with 73% for patients who received higher doses. In eight patients, treatment failed within the irradiated volume: all had received doses of less than 6,000 cGy, and the volume in three was judged to be inadequate.     

Motivations and Barriers to Routine HIV Testing Among Men Who Have Sex with Men in New York City

AIDS and Behavior - In-depth qualitative interviews explored the experiences and understandings of men 18–39&nbsp;years old who have sex with men that could facilitate or prevent HIV...     

Liquid‐Crystalline Nano‐optomechanical Actuator

The synthesis and characterization of organic nanoparticles composed of a polymer network of azobenzene moieties and capable of reproducible, photoinduced mechanical actuation are reported. The molecules within the nanoparticles undergo co‐ordinated, reversible isomerization between cis‐ and trans‐conformations in response to ultraviolet and visible electromagnetic radiation, resulting in a reversible 20% height contraction of nanoparticles adsorbed on a substrate. The kinetics of the actuation response as a function of light intensity and duration are reported and closely match the molecular kinetics of azobenzene photoisomerization. The results support the proposed mechanism of co‐ordinated molecular conformational changes resulting in observable nanoscale actuation.     

Hypertension and erectile dysfunction: The role of endovascular therapy in Asia

The prevalence of erectile dysfunction (ED) is above 40% in both Asian and non‐Asian male populations after the age of 40 years. The prevalence of ED among hypertensive patients is approximately double than that in normotensive population. Pelvic arterial insufficiency is the predominant cause of ED in men aged over 50 years. Stenosis in any segment of the iliac–pudendal–penile arterial system, which is considered an erectile‐related arterial axis, could lead to ED. Pharmacotherapy with lifestyle modification is effective in alleviating sexual dysfunction, yet a substantial number of patients still develop ED. Given the established applicability of angioplasty for the entire iliac–pudendal–penile arterial system, penile duplex ultrasound, and pelvic computed tomography angiography could be considered as the routine screening tools in ED patients with poor response to phosphodiesterase‐5 inhibitors. Endovascular therapy for pelvic arterial insufficiency‐related ED has been shown to be a safe and effective treatment option in patients who have anatomically suitable vessels and functionally significant stenoses. Clinical improvement was achieved in over 60% of patients at one year following pelvic angioplasty in the PERFECT registry from Taiwan. A 30%‐40% restenosis rate in distal internal pudendal and penile arteries remains a hurdle. Angioplasty for pelvic arterial occlusive disease could be considered as a viable approach to arteriogenic ED.     

High frequency of Fredrickson's phenotypes IV and IIb in Brazilians infected by human immunodeficiency virus

Background  

Human immunodeficiency virus (HIV) infection is very prevalent in Brazil. HIV therapy has been recently associated with coronary heart disease (CHD). Dyslipidemia is a major risk factor for CHD that is frequently described in HIV positive patients, but very few studies have been conducted in Brazilian patients evaluating their lipid profiles.     

Etoposide causes illegitimate V(D)J recombination in human lymphoid leukemic cells

Etoposide is one of the most widely used antineoplastics. Unfortunately, the same treatment schedules associated with impressive efficacy are associated with an increased risk of secondary acute myeloid leukemia (AML), which has prompted its withdrawal from some treatment regimens, thereby potentially compromising efficacy against the original tumor. Because etoposide-associated AML is characterized by site-specific illegitimate DNA recombination, we studied whether etoposide could directly cause site-specific deletions of exons 2 and 3 in the hprt gene. Human lymphoid CCRF-CEM cells were treated with etoposide for 4 hours, and DNA was isolated after subculturing. The deletion of exons 2 and 3 from hprt was assayed by a quantitative polymerase chain reaction (PCR) method. In the absence of etoposide treatment, the frequency of deletions of exons 2 and 3 was very low (5.05 x 10(-8)). After exposure to 10 mumol/ L etoposide, the frequency of the exon 2 + 3 deletion was increased immediately after and at 24 hours after etoposide treatment (65 to 89 x 10(-8)) and increased to higher levels (128 to 173 x 10(-8)) after 2 and 6 days of subculture (P < .001 overall). The frequency of the exon 2 + 3 deletion assessed at 6 days of subculture after 4 hours of 0, 0.25, 1, 2.5, 5, and 10 mumol/L etoposide treatment increased with etoposide concentration, ie, 5.05 x 10(-8), 89.2 x 10(-8), 108 x 10(-8), 142 x 10(-8), 163 x 10(-8), and 173 x 10(-8), respectively (P < .0001). Sequencing of a subset of amplified products confirmed the presence of DNA sequences at the breakpoints consistent with V(D)J recombination. By contrast, exon 2 + 3 deletions after etoposide treatment in the myeloid cell lines KG-1A and K562 showed no evidence of V(D)J recombinase in their genesis. We conclude that etoposide can induce the illegitimate site-specific action of V(D)J recombinase on an unnatural DNA substrate after a single treatment in human lymphoid cells.     

Seven‐action approaches for the management of hypertension in Asia – The HOPE Asia network

Asia is a large continent and there is significant diversity between countries and regions. Over the last 30 years, absolute blood pressure (BP) levels in Asia have increased to a greater extent than those in other regions. In diverse Asia‐Pacific populations, for choosing an Asia‐specific approach to hypertension management is important to prevent target organ damage and cardiovascular diseases. In this consensus document of HOPE Asia Network, we introduce seven action approaches for management of hypertension in Asia.     

Systemic antimicrobials in the treatment of chronic periodontal diseases: a dilemma

The use of systemic antimicrobials in the treatment of acute and chronic periodontal diseases must be viewed as a dilemma. On the one hand, the approach is attractive because of the microbial nature of periodontal diseases but, on the other hand, evidence of benefit of these agents is equivocal for the majority of periodontal diseases and antimicrobials have the potential to cause harm. The disadvantages of systemic antimicrobials can be grouped under the headings of allergic reactions, superinfection, toxicity, drug interactions, patient compliance and, perhaps of most widespread importance, bacterial resistance. Mechanical debridement methods, including drainage of pus for acute periodontal abscesses, should be considered the first line treatment for most periodontal diseases. Systemic antimicrobials should be considered as adjuncts to mechanical debridement methods and, in chronic disease, never used alone as they can predispose to abscess formation. Adjunctive systemic antimicrobials may be considered in acute disease where debridement or drainage of pus is difficult, where there is local spread or systemic upset. In chronic periodontal diseases, adjunctive antimicrobials should be considered in early onset or rapidly progressive disease or in advanced chronic adult disease where mechanical therapies have failed or surgery is not a preferred option. Inadequate oral hygiene and tobacco smoking are contra-indications to the use of antimicrobials. The value of systemic antimicrobials, where other systemic risk factors co-exist, has still to be established. The role of microbial diagnosis and sensitivity testing for antimicrobial selection at this time must be questioned.