Venous thromboembolism in the outpatient setting

BACKGROUND: There has been great interest in optimizing prophylaxis against venous thromboembolism (VTE) in the hospital setting. However, data from earlier studies suggest that most VTEs occur in the outpatient setting. The purposes of this observational study were to describe the frequency of VTEs occurring in the outpatient setting, characterize the prevalence of previously identified risk factors for VTE, and identify previous use of VTE prophylaxis. METHODS: The medical records of residents from the Worcester metropolitan area diagnosed as having International Classification of Diseases, Ninth Revision codes consistent with possible VTE during 1999, 2001, and 2003 were independently validated and reviewed by trained abstractors. RESULTS: A total of 1897 subjects had a confirmed episode of VTE. In all, 73.7% of patients developed VTE in the outpatient setting; a substantial proportion of these patients had undergone surgery (23.1%) or hospitalization (36.8%) in the preceding 3 months. Among these patients, 67.0% experienced VTE within 1 month of the preceding hospital encounter. Other major risk factors for VTE in the outpatient setting included active malignant neoplasm (29.0%) or previous VTE (19.9%). Among 516 patients with a recent hospitalization who subsequently developed VTE, less than half (42.8%) had received anticoagulant prophylaxis for VTE during that visit. CONCLUSIONS: More VTEs were diagnosed in the 3 months following hospitalization than during hospitalization. Efforts to improve in-hospital use of VTE prophylaxis may help decrease the incidence of outpatient VTE. However, given the shortening of hospital stays, studies of extended VTE prophylaxis following hospital discharge are warranted.     

A soluble ectodomain of LRIG1 inhibits cancer cell growth by attenuating basal and ligand-dependent EGFR activity

Leucine-rich repeats and immunoglobulin-like domains-1 (LRIG1) is a transmembrane protein with an ectodomain containing 15 leucine-rich repeats (LRRs) homologous to mammalian decorin and the Drosophila kekkon1 gene. In this study, we demonstrate that a soluble ectodomain of LRIG1, containing only the LRRs, inhibits ligand-independent epidermal growth factor receptor (EGFR) activation and causes growth inhibition of A431, HeLa and MDA-468 carcinoma cells. In contrast, cells that do not express detectable levels of EGFR fail to respond to soluble LRIG1. However, when a functional EGFR gene is introduced in these cells, they become growth-inhibited by soluble LRIG1 protein. Furthermore, we demonstrate the existence of high-affinity (K(d)=10 nM) binding sites on the A431 cells that can be competitively displaced (up to 75%) by molar excess of EGF. Even more powerful effects are obtained with a chimeric proteoglycan harboring the N-terminus of decorin, substituted with a single glycosaminoglycan chain, fused to the LRIG1 ectodomain. Both proteins also inhibit ligand-dependent activation of the EGFR and extracellular signal-regulated protein kinase 1/2 signaling in a rapid and dose-dependent manner. These results suggest a novel mechanism of action evoked by a soluble ectodomain of LRIG1 protein that could modulate EGFR signaling and its growth-promoting activity. Attenuation of EGFR activity without physical downregulation of the receptor could represent a novel therapeutic approach toward malignancies in which EGFR plays a primary role in tumor growth and survival.     

The role of surgery in the management of older women with breast cancer

Standard treatment for early breast cancer usually involves multi-modality treatment with a combination of surgery and one or more adjuvant therapies. These may include chemotherapy, radiotherapy, endocrine therapy and Trastuzumab. The treatment schedule for an individual patient may be complex, prolonged and associated with significant morbidity. The benefits of such regimens are clear to see in the improving mortality statistics for this breast cancer. However, such protocols may not appropriate for all women. Older women (over 70 years) have increasing rates of co-morbidities, reduced life expectancy and generally have more favourable breast cancer disease biology. Competing causes of death mean that they are less likely to die of their breast cancer, stage for stage, than a younger woman. In addition, their tolerance to some of the therapies is reduced which increases treatment related morbidity and reduces the risk to benefit ratio. It may therefore be appropriate to modify treatment protocols in selected older women. This should be done in consultation with the multi-disciplinary team with input from specialists in Medicine for the Elderly. The views and wishes of the patient should be respected during these discussions. This article reviews these issues.     

Randomised trial of drains versus no drains following radical hysterectomy and pelvic lymph node dissection: a European Organisation for Research and Treatment of Cancer-Gynaecological Cancer Group (EORTC-GCG) study in 234 patients

Drainage, following radical hysterectomy and pelvic lymph node dissection to prevent postoperative lymphocyst formation and surgical morbidity, is controversial. To study the clinical significance of drainage, 253 patients were registered and 234 patients were randomised into two arms. In one arm (n=117) postoperative drainage was performed, in the other arm (n=117) no drains were inserted. In both arms closure of the peritoneum of the operating field was omitted. The main exclusion criteria were blood loss of more than 3000 ml during surgery or persistent oozing at the end of the operation. Clinical and ultrasound or CT-scan evaluation was done at one and 12 months postoperatively. The median follow-up amounted to 13.3 months. No difference in the incidence of postoperative lymphocyst formation or postoperative complications was found between the two study arms. The late (12 months) incidence of symptomatic lymphocysts was 3.4% (drains: 5.9%; no drains: 0.9%). The difference showed a p-value of 0.06 in Fisher's Exact test. The operating time was related to the occurrence of postoperative lymphocyst formation. It was concluded that drains can be safely omitted following radical hysterectomy and pelvic node dissection without pelvic reperitonisation in patients without excessive bleeding during or oozing at the end of surgery.     

Resolution of eating disorders after right temporal lesions

We report two patients whose eating disorder resolved after right temporal lobe lesions. The first case report involves a woman with a history of bulimia nervosa and partial seizures arising from the occipital and right temporal regions. The second case is a woman with a history of anorexia nervosa that resolved after a head injury that resulted in right-sided inferofrontal and temporal encephalomalacia. Not only did both patients' eating disorders resolve, but their moods and libidos improved.