Recurrent giant cell tumor of long bones: analysis of surgical management

Treatment of giant cell tumor of bone (GCT) often is complicated by local recurrence. Intralesional curettage is the standard of care for primary GCTs. However, there is controversy whether intralesional curettage should be preferred over wide resection in recurrent GCTs.

[Should we screen and treat subclinical hypothyroidism?]

Subclinical hypothyroidism, defined as an elevated thyroid stimulating hormone and normal thyroxine level, is common with aging, particularly after 65 years old. This condition is potentially associated with important consequences, such as cardiovascular diseases and cognitive disorders. So far, indications for screening and thyroxine replacement therapy are still controversial. In this review, we examine the data on those risks and the potential benefits of the treatment. We also present a large European randomized clinical trial that should clarify this controversy, in order to improve clinical care of patients with subclinical hypothyroidism and to give reliable data on maintaining good health among the elderly.

What is the evidence supporting the prevention of osteoarthritis and improved femoral coverage after shelf procedure for Legg-Calvé-Perthes disease?

The evidence supporting continued use of shelf acetabuloplasty in Legg-Calvé-Perthes disease (LCPD) is not well-defined, and there is controversy regarding the long-term benefits related to clinical and functional improvement.

National institutes of health stroke scale score and vessel occlusion in 2152 patients with acute ischemic stroke

Background and Purpose—There is some controversy on the association of the National Institutes of Health Stroke Scale (NIHSS) score to predict arterial occlusion on MR arteriography and CT arteriography in acute stroke. Methods—We analyzed NIHSS scores and arteriographic findings in 2152 patients (35.4% women, mean age 66±14 years) with acute anterior or posterior circulation strokes. Results—The study included 1603 patients examined with MR arteriography and 549 with CT arteriography. Of those, 1043 patients (48.5%; median NIHSS score 5, median time to clinical assessment 179 minutes) showed an occlusion, 887 in the anterior (median NIHSS score 7/0–31), and 156 in the posterior circulation (median NIHSS score 3/0–32). Eight hundred sixty visualized occlusions (82.5%) were located centrally (ie, in the basilar, intracranial vertebral, internal carotid artery, or M1/M2 segment of the middle cerebral artery). NIHSS scores turned out to be predictive for any vessel occlusions in the anterior circulation. Best cut-off values within 3 hours after symptom onset were NIHSS scores ≥9 (positive predictive value 86.4%) and NIHSS scores ≥7 within >3 to 6 hours (positive predictive value 84.4%). Patients with central occlusions presenting within 3 hours had NIHSS scores <4 in only 5%. In the posterior circulation and in patients presenting after 6 hours, the predictive value of the NIHSS score for vessel occlusion was poor. Conclusions—There is a significant association of NIHSS scores and vessel occlusions in patients with anterior circulation strokes. This association is best within the first hours after symptom onset. Thereafter and in the posterior circulation the association is poor.

Angioembolization for pelvic hemorrhage control: results from the German pelvic injury register

Hemorrhage from pelvic vessels is a potentially lethal complication of pelvic fractures. There is ongoing controversy on the ideal treatment strategy for patients with pelvic hemorrhage. The aim of the study was to analyze the role of angiography and subsequent embolization in patients with pelvic fractures and computed tomography scan-proven vascular injuries.

Modulation of L-α-lysophosphatidylinositol/GPR55 mitogen-activated protein kinase (MAPK) signaling by cannabinoids

GPR55 is activated by l-α-lysophosphatidylinositol (LPI) but also by certain cannabinoids. In this study, we investigated the GPR55 pharmacology of various cannabinoids, including analogues of the CB1 receptor antagonist Rimonabant®, CB2 receptor agonists, and Cannabis sativa constituents. To test ERK1/2 phosphorylation, a primary downstream signaling pathway that conveys LPI-induced activation of GPR55, a high throughput system, was established using the AlphaScreen® SureFire® assay. Here, we show that CB1 receptor antagonists can act both as agonists alone and as inhibitors of LPI signaling under the same assay conditions. This study clarifies the controversy surrounding the GPR55-mediated actions of SR141716A; some reports indicate the compound to be an agonist and some report antagonism. In contrast, we report that the CB2 ligand GW405833 behaves as a partial agonist of GPR55 alone and enhances LPI signaling. GPR55 has been implicated in pain transmission, and thus our results suggest that this receptor may be responsible for some of the antinociceptive actions of certain CB2 receptor ligands. The phytocannabinoids Δ9-tetrahydrocannabivarin, cannabidivarin, and cannabigerovarin are also potent inhibitors of LPI. These Cannabis sativa constituents may represent novel therapeutics targeting GPR55.

Predictors of short term treatment outcome in patients with achalasia following endoscopic or surgical therapy

Pneumatic balloon dilation and surgical myotomy are the most effective treatments for achalasia. While there is controversy which method is best, the aim of the current study was to identify predictors of symptom recurrence after endoscopic or surgical therapy.

A clinical approach to arterial ischemic childhood stroke: increasing knowledge over the last decade

Childhood stroke is increasingly being recognized as an important burden not only for affected children and families, but also for socioeconomic reasons. A primary problem is delayed diagnosis, due to the many mimics of childhood stroke, and the variety of manifesting symptoms. The most important is hemiparesis (with/without dysphasia or facial palsy), but ataxia, seizures, and many more are also possible. Suspicion of stroke has to be ascertained by neuroimaging, gold standard being (diffusion weighted) magnetic resonance. Risk factors are multiple, but their presence might help to increase the suspicion of stroke. The most important factors are infectious/parainfectious etiologies, frequently possibly manifesting by transient focal cerebral arteriopathy (FCA). Cardiological underlying problems are the second most important. Arteriopathies can be detected in about half of the children, besides FCA and dissection and MoyaMoya disease are the most important. Hereditary coagulopathies increase the risk of stroke. There is still a controversy on best treatment in children: platelet antiaggregation and heparinization are used about equally. Thrombolysis is being discussed increasingly. Severity of symptoms at manifestation and on follow-up are not less significant in children than in young adults. About two-third of the children have significant residual neurological problems and a majority cognitive and behavior problems.

ABO histo-blood group antigen expression on the graft endothelium long term after ABO-compatible, non-identical heart transplantation

We recently reported a complete change in the endothelial ABO histo-blood group phenotype of a cardiac allograft long term after B to O mismatched transplantation. In the context of the current controversy on graft recolonization with recipient endothelial cells and its importance in the development of immunological unresponsiveness, we monitored the expression of endothelial ABH histo-blood group antigens of 10 ABO-compatible, non-identical cardiac allografts over an observation period of at least 30 months. ABH antigens as well as markers for endothelial cells, erythrocytes and thrombocytes were investigated retrospectively by immunohistochemistry using monoclonal antibodies on sections of formalin-fixed, paraffin-embedded biopsies and were evaluated semi-quantitatively by microscopy. In contrast to our earlier finding of the change in the endothelial ABO histo-blood group phenotype long term after ABO- mismatched transplantation, we could not confirm this change in 10 compatible but non-identical cases.

Is Pelvic Lymph Node Dissection Necessary in Patients with a Serum PSA<10ng/ml Undergoing Radical Prostatectomy for Prostate Cancer?

OBJECTIVE: Controversy persists concerning the role of pelvic lymph node dissection (PLND) in patients with preoperative PSA values <10ng/ml undergoing treatment for prostate cancer with a curative intent. The aim of this study was to determine the incidence of lymph node metastasis in this subgroup of patients. METHODS: Patients with clinically localized prostate cancer and a serum PSA<10ng/ml, without neoadjuvant hormonal or radiotherapy, with negative staging examinations who underwent radical retropubic prostatectomy with bilateral extended PLND and with >/=10 lymph nodes detected by the pathologist in the surgical specimen, were included in the study. RESULTS: A total of 231 patients with a median serum PSA of 6.7ng/ml (range 0.4-9.98) and a median age of 62 years (range 44-76) were evaluated. A median of 20 (range 10-72) nodes were removed per patient. Positive nodes were found in 26 of 231 patients (11%), the majority of which (81%) had a Gleason score >/=7 in the surgical specimen. Of the patients with a Gleason score >/=7 in the prostatectomy specimen 25% had positive nodes, whereas only 3% with a Gleason score /=7 in the prostatectomy specimen was 25% after extended PLND. It seems that in this patient group extended PLND, including removal of nodes along the internal iliac vessels, is warranted.

Origin and prognostic value of circulating KRAS mutations in lung cancer patients

Because of the current controversy on the origin and clinical value of circulating KRAS codon 12 mutations in lung cancer, we screened 180 patients using a combined restriction fragment-length polymorphism and polymerase chain reaction (RFLP-PCR) assay. We detected KRAS mutations in 9% plasma samples and 0% matched lymphocytes. Plasma KRAS mutations correlated significantly with poor prognosis. We validated the positive results in a second laboratory by DNA sequencing and found matching codon 12 sequences in blood and tumor in 78% evaluable cases. These results support the notion that circulating KRAS mutations originate from tumors and are prognostically relevant in lung cancer.

[Photodynamic therapy of AMD for the first (better sight) and the second (worse sight) eyes]

BACKGROUND: Photodynamic therapy (PDT) is the standard treatment procedure for many forms of exudative and/or neovascular AMD. Despite therapy, visual acuity often drops to low vision levels. The cost efficiency of treating the eye in which vision is worse is therefore the subject of some controversy. PATIENTS AND METHODS: A retrospective case-control study was conducted in all patients who were treated with PDT at the Universitätsspital Zürich between September 1999 and November 2004. Each patient's first (with worse vision) and second (with better vision) eyes were compared for situation on presentation and course during treatment. RESULTS: In 117/228 cases (51.3%) visual acuity of the treated eye was better than (or identical to) that of the fellow eye at presentation. Visual acuity before therapy was an average of 0.58+/-0.27 logMAR [Snellen: 0.26 (0.14-0.49)] in the eyes with better visual acuity and 0.69+/-0.4 logMAR [Snellen 0.20 (0.08-0.51)] in the fellow eyes (p=0.015). After therapy there was no significant difference between the patient groups in visual acuity or in the magnitude of any change in visual acuity, or in lesion size or change in lesion size. CONCLUSION: The outcome of PDT of a second eye (with better visual acuity) is not significantly better than the result obtained in the first eye (the one with worse visual acuity initially).

Thrombosis and drug-eluting stents: an objective appraisal

Stent thrombosis (ST) after percutaneous coronary intervention has been the focus of intense interest because of its attendant morbidity and mortality. There is controversy about several facets of the problem. These include the frequency of ST with drug-eluting stents (DES) versus bare-metal stents (BMS), the timing of the event, clinical consequences, risk factors, adjunctive therapy, and new preventive approaches. Information has accrued rapidly from several sources, including randomized controlled clinical trials of DES versus BMS in carefully selected subsets of patients and registry experiences in larger patient groups, which provide a more universal real-world picture. The results from these different data sets are not completely concordant. However, several general conclusions can be made: 1) ST is an infrequent but very severe complication of both BMS and DES; 2) at the present time, during 4 years of follow-up from randomized controlled trials that compared DES and BMS, there is no apparent difference in overall ST frequency, although the time course for occurrence appears to differ, with a relative numeric excess of ST late after DES implant; 3) despite this relative imbalance, no differences in the end points of death or death and infarction between DES and BMS are observed; 4) longer-term follow-up of these patients as well as larger angiographic and clinical subsets of patients who receive this technology outside of randomized trials are required to fully study this issue; and 5) advances in stent platforms for drug elution as well as adjunctive pharmacologic therapy are being evaluated to enhance long-term safety.

Extracapsular tumor spread and the risk of local, axillary and supraclavicular recurrence in node-positive, premenopausal patients with breast cancer

BACKGROUND: Extracapsular tumor spread (ECS) has been identified as a possible risk factor for breast cancer recurrence, but controversy exists regarding its role in decision making for regional radiotherapy. This study evaluates ECS as a predictor of local, axillary, and supraclavicular recurrence. PATIENTS AND METHODS: International Breast Cancer Study Group Trial VI accrued 1475 eligible pre- and perimenopausal women with node-positive breast cancer who were randomly assigned to receive three to nine courses of classical combination chemotherapy with cyclophosphamide, methotrexate, and fluorouracil. ECS status was determined retrospectively in 933 patients based on review of pathology reports. Cumulative incidence and hazard ratios (HRs) were estimated using methods for competing risks analysis. Adjustment factors included treatment group and baseline patient and tumor characteristics. The median follow-up was 14 years. RESULTS: In univariable analysis, ECS was significantly associated with supraclavicular recurrence (HR = 1.96; 95% confidence interval 1.23-3.13; P = 0.005). HRs for local and axillary recurrence were 1.38 (P = 0.06) and 1.81 (P = 0.11), respectively. Following adjustment for number of lymph node metastases and other baseline prognostic factors, ECS was not significantly associated with any of the three recurrence types studied. CONCLUSIONS: Our results indicate that the decision for additional regional radiotherapy should not be based solely on the presence of ECS.

Meta-analysis in medical research: potentials and limitations

Meta-analysis, the statistical combination of results from several studies to produce a single estimate of a treatment effect or size of an association, continues to attract controversy. We illustrate and discuss the promises and limitations of meta-analysis. Meta-analysis of clinical trials can prevent delays in the introduction of effective treatments or lead to the timely identification of adverse effects. However, meta-analyses are liable to numerous biases, both at the level of the individual study and the selection of studies for inclusion in meta-analysis. The biases and confounding factors that threaten the validity of individual studies will also affect meta-analyses of observational studies. We argue that meta-analyses should only be performed within the framework of systematic reviews that have been prepared using methods that minimize bias and address the combinability of studies.