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Background: Weight gain is a negative prognostic factor in breast cancer (BC) patients. The risk factors for weight gain during adjuvant endocrine therapy (ET) and the extent to which such weight gain is associated with disease recurrence remain unclear., Patients and Methods: We retrospectively identified a cohort of women with a diagnosis of stage I-III, hormone receptor-positive, human epidermal growth factor receptor 2-negative BC from January 1997 to August 2008, who had received initial treatment at the MD Anderson Cancer Center, had completed 5 years of ET, and had remained free of locoregional or distant relapse or contralateral BC for ≥ 5 years after diagnosis. The weight change at the end of 5 years of ET was measured as the percentage of the change in weight from the start of ET, with a weight gain of > 5% considered clinically significant. Multivariable logistic regression and Cox proportional hazards models were used to assess the determinants of such weight gain and the risk of recurrence after 5 years., Results: Of 1282 long-term BC survivors, 432 (33.7%) had a weight gain of > 5% after 5 years of ET. Women who were premenopausal at diagnosis were 1.40 times more likely than women who were postmenopausal at diagnosis to have a weight gain of > 5%. Asian women had the lowest risk of gaining weight. The recurrence risks of patients who had gained weight and those who had not were not significantly different., Conclusion: Premenopausal BC patients had an increased risk of weight gain after 5 years of ET; however, BC patients with a weight gain of > 5% did not have an increased risk of disease recurrence., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: It is estimated that millions of North Americans would qualify for lung cancer screening and that billions of dollars of national health expenditures would be required to support population-based computed tomography lung cancer screening programs. The decision to implement such programs should be informed by data on resource utilization and costs., Methods: Resource utilization data were collected prospectively from 2059 participants in the Pan-Canadian Early Detection of Lung Cancer Study using low-dose computed tomography (LDCT). Participants who had 2% or greater lung cancer risk over 3 years using a risk prediction tool were recruited from seven major cities across Canada. A cost analysis was conducted from the Canadian public payer's perspective for resources that were used for the screening and treatment of lung cancer in the initial years of the study., Results: The average per-person cost for screening individuals with LDCT was $453 (95% confidence interval [CI], $400-$505) for the initial 18-months of screening following a baseline scan. The screening costs were highly dependent on the detected lung nodule size, presence of cancer, screening intervention, and the screening center. The mean per-person cost of treating lung cancer with curative surgery was $33,344 (95% CI, $31,553-$34,935) over 2 years. This was lower than the cost of treating advanced-stage lung cancer with chemotherapy, radiotherapy, or supportive care alone, ($47,792; 95% CI, $43,254-$52,200; p = 0.061)., Conclusion: In the Pan-Canadian study, the average cost to screen individuals with a high risk for developing lung cancer using LDCT and the average initial cost of curative intent treatment were lower than the average per-person cost of treating advanced stage lung cancer which infrequently results in a cure.

The most frequent head injuries resulting from bicycle accidents include skull fracture acute subdural hematoma (ASDH), cerebral contusions, and diffuse axonal injury (DAI). This review includes epidemiological studies, cadaver experiments, in vivo imaging, image processing techniques, and computer reconstructions of cycling accidents used to estimate the mechanical parameters leading to specific head injuries. The results of the head impact tests suggest the existence of an energy failure level for the skull fracture, specific for different impact regions (22-24J for the frontal site and 5-15J for temporal site). Typical linear patterns were described for frontal, parietal and occipital skull fracture. Temporal skull fracture described considerably higher variability. In term of contusion mechanogenesis, the experiments proved that relative brain-skull motion will not be prevented if the maximum frequency of the impact frequency spectrum stays below 150Hz or below the frequency corresponding to the impedance peak of the head under investigation. The brain shift patterns in humans, both in dynamic and quasistatic situations were shown to be very complex, with maximum amplitudes localized at the level of the inferolateral aspects of the frontal and temporal lobes. The resulting brain maximum amplitudes differed when the head was subjected to a sagittal or lateral motion. Finally, the presented data support the existence of a critical elongation/stretch criterion for the occurrence of ASDH due to BV rupture, located around 5mm elongation or 25% stretch limit. In addition, a tolerance level lying around 10,000rad/s(2) for pulse durations below 10ms was established for BV rupture, which seems to decrease with increasing pulse duration. The described research indicates that injury specific tolerance criteria can provide a more accurate prediction for head injuries than the currently used HIC. Internal brain lesions are strongly related to rotational effects which are not appropriately accounted by the commonly accepted head injury criterion (HIC). The research summarized in this paper adds significantly to the creation of a fundamental knowledge for the improvement of bicycle helmets as well as other head protective measures. The described investigations and experimental results are of crucial importance also for forensic research., (© 2013 Elsevier Ltd. All rights reserved.)

Background: Traumatic brain injury is expected to become the major cause of death and disability for children and young adults by the year 2020. One of the most frequent and most morbid pathologies resulted from a head trauma is acute subdural haematoma (ASDH). For nearly one third of the ASDH cases the etiopathology directly relates to a bridging vein (BV) rupture., Methods: In the current study the bridging vein-superior sagittal sinus (BV-SSS) units were axially stretched until failure for strain rates ranging from 2.66s(-1) to 185.61s(-1), in order to investigate any strain rate dependency in their mechanical behaviour., Findings: Results showed that up to 200s(-1), the effect of the strain rate on veins' mechanical behaviour is outweighed by the large morphological intra- and inter-individual variations. Gender had a strong influence on the BVs geometrical description, but exerted no direct influence on the BV biomechanical parameters. Veins' dimensions had the strongest influence on the BV mechanical behaviour and on the failure mechanism., Interpretation: The present study brings important contribution to the ASDH research, emphasising the importance of considering the BV-SSS complex as a whole when trying to describe the ASDH mechanopathology., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Introduction: Non-small cell lung cancer (NSCLC) frequently presents at an incurable stage, and a majority of patients will be considered for palliative chemotherapy at some point in their disease. This article reviews the growing evidence for first-line treatment in NSCLC., Methods: Studies of first-line chemotherapy regimens including new agents (docetaxel, gemcitabine, irinotecan, paclitaxel, pemetrexed, and vinorelbine) and targeted agents (bevacizumab, erlotinib, and gefitinib) were identified through Medline, Embase, the Cochrane databases, and web sites of guideline organizations., Results: Two evidence-based guidelines, 10 systematic reviews, and forty-six randomized trials were eligible for inclusion. Randomized studies suggest that platinum-based doublets (platinum plus new agent) are the standard of care for first-line systemic therapy. No one new agent is clearly superior for use in combination with a platinum agent. The survival advantage of platinum-based doublets over nonplatinum combinations or older combinations is modest. The addition of bevacizumab to carboplatin and paclitaxel has shown improved survival, although multiple exclusion criteria limit the applicability of these data to a subset of patients. In patients at least 70 years of age or with Eastern Collaborative Oncology Group performance status 2, a new single agent is an alternative. Treatment beyond four to six cycles impedes quality of life without prolonging life. Emerging data suggest that the choice of chemotherapy agent may be influenced by histologic subtype., Conclusion: In NSCLC, a combination of a platinum agent plus a new agent continues to be the standard of care. As differences between regimens are small, toxicity and patient preference should help guide regimen choice.

Background: Elevated levels of the cell cycle protein cyclin E, and low levels of its inhibitor, p27(Kip1), have been associated with a poor prognosis following breast cancer. Some studies have found that germline mutations in the breast cancer susceptibility gene, BRCA1, are also associated with an inferior survival rate. The relationship between cyclin E/p27(Kip1) levels, BRCA1 status and outcome has not been studied in detail., Patients and Methods: We analyzed a historical cohort of 288 Ashkenazi Jewish women who were diagnosed with breast cancer between 1980 and 1995 and were previously tested for BRCA1/2 mutations. Protein levels of cyclin E and p27(Kip1) were assessed by immunohistochemistry. Breast cancer-specific survival (BCSS) was the main outcome measured., Results: The median follow-up was 8 years. Thirty tumors carried germline BRCA1 mutations. These tumors were more likely to have high cyclin E protein levels [odds ratio (OR) 9.5; P <0.001] and low p27(Kip1) protein levels (OR 2.8; P=0.03) than tumors from patients without BRCA1/2 mutations. High cyclin E expression level was the strongest predictor of BRCA1 germline mutations (multivariate OR 4.7; P=0.004). On univariate analysis, high cyclin E protein levels [relative risk (RR) 2.6; P <0.001] and low p27(Kip1) protein levels (RR 2.3; P=0.006) were significant prognostic factors for a poorer BCSS. In Cox multivariate models, high cyclin E levels remained an independent indicator of poor outcome only in the subgroup of patients who did not receive chemotherapy (P=0.002)., Conclusions: In this ethnically restricted cohort, a high level of cyclin E is a characteristic of BRCA1-related breast cancer, and is a marker of poor prognosis following breast cancer, particularly in the absence of adjuvant chemotherapy.

Background: We determined whether physicians involved in a clinical trial adhere to the study recommendations or the stated policy of their treatment centre with respect to the administration of boost radiation after breast conserving surgery., Patients and Methods: Boost radiation treatment policy was determined by survey at 25 oncology centres involved in a randomised trial of breast or breast plus nodal radiation in Canada. Actual practice was compared with stated policy and study recommendations., Results: Among 248 subjects, 201 (81%) were treated according to stated policy [kappa=0.40, 95% confidence intervals (CI) 0.27-0.52; P<0.0001], indicating only a fair to moderate agreement between stated and actual practice, while 232 (94%) were treated according to study recommendations (kappa=0.59, 95% CI 0.40-0.77; P<0.0001), indicating moderate to near substantial agreement between study recommendations and actual practice (P=0.88 for z-test of difference). In a multivariate analysis, subjects who had invasive disease at a resection margin were more likely to get a boost than those with margins clear of invasive tumour by 2 mm [odds ratio (OR) 49, 95% CI 7.6-322; P<0.0001]., Conclusions: Physicians appear compliant with study recommendations for a non-randomised manoeuvre in a clinical trial, possibly at the expense of compliance with stated local policy. Clinical trial protocols should incorporate standard practice., (Copyright 2004 European Society for Medical Oncology)

Background: DNA methylation is the addition of a methyl group to the 5 position of cytosine. It is an epigenetic process with several effects, including chromatin structure modulation, transcriptional repression and the suppression of transposable elements. In malignancy, methylation patterns change, resulting in global hypomethylation with regional hypermethylation. This can lead to genetic instability and the repression of tumor suppressor genes., Design: A review of the DNA methyltransferase inhibitor literature was conducted., Results: DNA methylation inhibitors have demonstrated the ability to inhibit hypermethylation, restore suppressor gene expression and exert antitumor effects in in vitro and in vivo laboratory models. Four inhibitors, which are analogs of the nucleoside deoxycitidine, have been clinically tested: 5-azacytidine, 5-aza-2'-deoxycytidine, 1-beta-D-arabinofuranosyl-5-azacytosine and dihydro-5-azacytidine. The first two have demonstrated encouraging antileukemic activity but little activity in solid tumors, while the latter two are no longer under study due to lack of efficacy. A fifth agent, MG98, is an antisense oligodeoxynucleotide directed against the 3' untranslated region of the DNA methyltransferase-1 enzyme mRNA, and is now under phase II study., Conclusions: While some positive clinical results with DNA methyltransferase inhibitors have been seen, a definitive clinical role for these agents will most likely require combination therapy, and good phase III studies are needed.

Background: The technique of posterior fossa decompression, nowadays preferred by most neurosurgeons as the first surgical option in the treatment of hindbrain associated syringomyelia, was reintroduced in our center in 1989. We present a retrospective analysis of 22 patients with this pathology who underwent the procedure since then., Methods: In all patients diagnosis was made by MRI of the craniospinal junction. The operation consisted of a suboccipital craniectomy, removal of the posterior arc of C1, laminectomy of C2 or C3 when necessary and a wide duraplasty at the end. The intradural manipulations (opening of the arachnoid membrane, coagulation or resection of the tonsils) were not uniform. Postoperatively short- and long-term clinical outcome and MRI findings were assessed., Results: Sixteen out of 21 patients (76%) experienced an improvement in the early follow-up period. In the late follow-up period 13 out of 19 patients (68%) were improved, whereas five patients (26%) experienced a marked deterioration. There was no unequivocal effect on all symptoms and signs. Postoperative MR images showed a favorable result in 16 out of 20 patients (80%), consisting of syrinx collapse or reduction of the syrinx diameter., Conclusions: We conclude that decompression of the posterior fossa is a safe procedure with a considerable chance of clinical improvement. Although total syrinx collapse is not as frequently seen as in syrinx shunting procedures, the clinical outcome may be better. Moreover, there seemed to be no unequivocal correlation between clinical outcome and postoperative syrinx size in the present study.

Three patients with a spontaneous spinal epidural hematoma are presented, one of which is exceptional because it could be attributed to thrombolysis with alteplase. The other two were correlated with oral anticoagulant therapy. Our second case suggests that Morbus Kahler may be an underlying pathology in spinal extradural hematoma. In the third patient neither an obvious 'locus minoris resistentiae' nor a pathological coagulation test could be held responsible for the spontaneous bleeding. All three patients underwent laminectomy and evacuation of the hematoma. Although two of our cases are examples of complete recuperation after late operative intervention, early surgery is preferable. Permanent clinical attention together with a low threshold to perform magnetic resonance imaging (MRI) leads to a quicker diagnosis of spinal epidural hematoma. We show that administration of gadolinium may facilitate correct preoperative localization of the hematoma because there may be contrast enhancement of the hematoma. Finally, the postoperative policy concerning thromboembolic prophylaxis is discussed.

Vertebral chordomas are rather rare tumours, especially in the lower cervical region. We present a patient with a C7 vertebral body chordoma and a discussion of pertinent literature is given. Only three C7 chordomas have been reported previously. Diagnosis is sometimes difficult to establish and is based on radiological examinations. Once the histological diagnosis is available, one should aim at a total resection. If this is not possible, adjuvant radiotherapy should be given. For limited cervical lesions, we advise a corporectomy with fusion by an iliac crest graft and osteosynthetic plate stabilisation.

A case of severe acute upper airway obstruction caused by a cervical osteophyte requiring urgent tracheostomy is presented. The patient was treated successfully by resection of the osteophyte followed by cervical fusion.

Microscopical lumbar discectomy is nowadays a very common neurosurgical procedure. The technique has been introduced more than 15 years ago. For the present study a series of 100 consecutive patients, operated upon by one surgeon and with a follow-up period of at least 1 year, was reviewed. The importance of a clean surgical indication is stressed. At the latest follow-up examination 3 patients still complained of moderately intense sciatica and 1 of backache of an invalidating degree. Four patients needed a second operation for a recurrent herniation at the same or another level. Eventually, 96 patients were able to resume their previous, if available, professional activities.

Juxta-facet cysts are relatively uncommon intraspinal lesions, causing radiculopathy, neurogenic claudication or myelopathy. To the best of our knowledge, only 4 cases of bilateral synovial or ganglioncysts were described. We report the 5th case of bilateral ganglioncysts of the lumbar spine. Generally, juxta-facet cysts should be differentiated from other intraspinal lesions, such as herniated discs, meningiomas and neurinomas. Correct preoperative diagnosis is necessary for adequate treatment, namely the (microscopic) resection of the cyst. After adequate treatment, complete recovery may be expected.

One hundred and fifteen patients with curative and palliative surgery for gastric cancer were randomized to receive radiotherapy alone (1) or in combination with short-term (ST) 5-FU (2), long-term (LT) 5-FU (3), ST and LT 5-FU (4). The ST 5-FU was given at a daily dose of 575 mg/m2, every 4-6 h during the first 4 days of treatment before starting irradiation. The LT 5-FU was given at a dosage of 750 mg/m2 every 2 weeks for 18 months or until progression. The median survival times for treatment 1 to 4 was respectively 12, 10, 15 and 18 months. There was a statistically significant overall difference between the four treatments (P = 0.041). However, when the comparisons were adjusted for the most significant prognostic factors, the difference in survival disappeared. Moreover, no difference was found between treatments in terms of time progression. Nevertheless, among 22 patients with residual tumour, the three who were still alive without disease progression (with survivals of 19+, 49+ and 90+ months at the time of this analysis) had been treated with radiotherapy combined with ST and LT 5-FU.

Glossopharyngeal neurinomas are rare entities. Only 16 cases have been described so far in the literature. Our experience with 2 cases demonstrates the non-specific and discrete clinical presentation of the ninth nerve neurinoma, but illustrates also some typical radiological aspects, enabling a more precise preoperative diagnosis. Two cases are presented and a survey of the literature is given.

Different types of anomalies of the lumbosacral nerve roots were documented in the literature. The present report is the first description of a combination of conjoined and anastomosed nerve roots, at the same level and unilaterally, in the lumbar region.

Since 1979 much attention has been payed in the literature to the presence and importance of estrogen- and progesterone-receptors in meningiomas. The existence of these receptors seems to be proven, but the question about their biological activity is not solved conclusively. If the hypothesis of a biological activity of the estrogen- and progesterone-receptors in meningiomas is confirmed, some patients could benefit from a hormonal therapy.