Subfascial endoscopic perforator vein surgery: who benefits?

The advent of minimally invasive endoscopic surgery has rekindled interest in perforator vein ligation. Subfascial endoscopic perforator vein surgery (SEPS) utilizes techniques to interrupt incompetent perforators under direct vision using an endoscopic videocamera and instrumentation placed through small ports remote from the active ulcer or area of diseased skin. The safety and early efficacy of SEPS has been established in several studies, and it yields lower wound complication rates than observed with open surgical techniques such as the Linton procedure. Available results confirm the superiority of SEPS over open perforator ligation, but do not address the its role in the surgical treatment of advanced chronic venous insufficiency (CVI) and venous ulceration. Ablation of superficial reflux by high ligation and stripping of the greater saphenous vein with avulsion of branch varicosities is concomitantly performed in the majority of patients undergoing SEPS. The clinical and hemodynamic improvements attributable to SEPS thus are difficult to ascertain. As with open perforator ligation, clinical and hemodynamic results are better in patients with primary valvular incompetence (PVI) than in those with the postthrombotic (PT) syndrome. Until prospective, randomized, multicenter clinical trials are carried out to answer lingering questions regarding the efficacy of SEPS, the procedure is recommended in patients with advanced CVI secondary to PVI of superficial and perforating veins, with or without deep venous incompetence. The performance of SEPS in patients with PT syndrome remains controversial.     

Abnormal bleeding in postmenopausal hormone users—What do we know today?

Whilst use of estrogen-containing hormone therapy (HT) has declined in recent years, it is still used by a significant minority of women and remains the most effective way of treating menopausal vasomotor symptoms and vaginal dryness. Unscheduled vaginal bleeding and spotting is a common unwanted effect of combined HT. This abnormal bleeding is inconvenient and commonly leads to invasive tests to exclude underlying pelvic pathology. The mechanisms underlying unscheduled bleeding with HT are poorly understood and there are no evidence-based treatment options. Relatively few studies have investigated how combined hormone therapy induces changes in the endometrium which may predispose to increased bleeding. The available evidence suggests that combined HT induces changes in endometrial blood vessels and stroma which may increase vascular fragility. An improved understanding of how combined HT changes the endometrium to induce bleeding may lead to targeted therapies to effectively prevent or resolve bleeding in postmenopausal women. This will improve the acceptability of combined HT and have personal benefits for postmenopausal women and financial benefits for healthcare providers. This review will discuss current evidence and potential mechanisms underlying unscheduled bleeding with combined HT.     

Local tolerance and systemic safety of pegaptanib sodium in the dog and rabbit.

PURPOSE: To evaluate the local tolerance, systemic toxicity, and toxicokinetics in dogs and rabbits of pegaptanib sodium, an aptamer that targets vascular endothelial growth factor (VEGF(165)). METHODS: Dogs received biweekly, bilateral, intravitreous (IVT) injections of pegaptanib sodium for 9 months at doses of 0.3 (n = 10), 1 (n = 10), or 3 mg (n = 14); 14 control dogs received phosphate-buffered saline (PBS). In rabbits, pegaptanib sodium was administered by IVT injection biweekly for 6 months at doses of 0.2 (n = 14), 0.67 (n = 14), or 2 mg (n = 18); 18 rabbits received PBS. The systemic and ocular safety of pegaptanib sodium was assessed. Assessments in both dogs and rabbits included complete ophthalmologic examinations, serum chemistry, hematology, urinalysis, and coagulation assessments, as well as gross and microscopic pathologic examination. In addition, dogs were assessed by electroretinography and electrocardiography. In a cardiovascular safety study, loading intravenous boluses and maintenance infusions of pegaptanib sodium or PBS were administered to dogs (n = 4) in an ascending dose design, with each dose level separated by 2-3 days. The pegaptanib dosing regimens were designed to achieve pegaptanib plasma concentrations of approximately 90, 270, or 900 ng/mL. RESULTS: There were no pegaptanib sodium-associated clinical, ophthalmologic, pathologic, or cardiovascular abnormalities at doses of pegaptanib that achieved systemic and ocular exposure levels in excess of those associated with the recommended pegaptanib IVT dosing regimen of 0.3 mg per study eye in patients with age-related macular degeneration. CONCLUSION: These studies, together with data from clinical trials, provide strong evidence that inhibition of VEGF(165) by pegaptanib in the eye is a safe therapy for the treatment of ocular neovascular disease.     

Giggle incontinence in children: a manifestation of detrusor instability

PURPOSE: To our knowledge the prevalence and cause of giggle incontinence in children is not known. We hypothesized that laughter may induce unstable detrusor contractions in children susceptible to detrusor instability. We evaluated the prevalence of diurnal voiding symptoms of urinary urgency, urge incontinence, pelvic withholding maneuvers and hesitancy in patients with giggle incontinence, the prevalence of giggle incontinence in patients with diurnal voiding symptoms, the prevalence of the 2 conditions in first degree relatives of patients with giggle incontinence, the influence of treatment for detrusor instability on the frequency of giggle incontinence and the prevalence of diurnal voiding symptoms in control children with giggle incontinence. MATERIALS AND METHODS: Of 1,421 children 5 to 15 years old referred to the pediatric nephrology department for various problems 109 were diagnosed with giggle incontinence and 460 had diurnal voiding symptoms. A total of 627 children visiting the pediatrician office whose parents completed a survey questionnaire served as controls. RESULTS: Diurnal voiding symptoms were noted in 95% of the patients with giggle incontinence, while giggle incontinence was noted in 23% of those with diurnal voiding symptoms. Of the patients with giggle incontinence a positive family history for that entity and diurnal voiding symptoms was noted in 13% and 28%, respectively. Giggle incontinence improved in all patients after treatment for detrusor instability and it resolved completely in 89%. Giggle incontinence recurred with a relapse of diurnal voiding symptoms in 28 cases and improved with improved diurnal voiding symptoms during modification of therapy. Diurnal voiding symptoms were present in 43% of the 157 controls with giggle incontinence. CONCLUSIONS: Giggle incontinence results from detrusor instability induced by laughter and it improves with effective treatment of detrusor instability.     

Basic fibroblast growth factor induces TGF-beta release in an isoform and glioma-specific manner

The aim of the current study was to determine whether basic fibroblast growth factor (bFGF), regulates the release of transforming growth factor-beta1 (TGF-beta1) from C6 glioma cells. The results of the study show that bFGF (2, 5 and 10 ng/ml) dose dependently induced the release of TGF-beta1 from C6 glioma cells, with the 10 ng/ml dose inducing a 2- to 3-fold increase of TGF-beta1 levels. This effect was evident as early as 6 h following treatment, with maximal levels observed at 18 h. The effect of bFGF was largely on latent TGF-beta1, and was isoform specific, as bFGF had no effect on TGF-beta2 release. The bFGF effect on TGF-beta1 was also glioma specific, as no such stimulatory effect was observed in rat cortical astrocytes.     

Primary mucosal malignant melanoma of the head and neck

INTRODUCTION: The relative rarity of mucosal melanomas of the head and neck (MMHN) has made analysis of treatment approaches difficult. Advances in diagnostic techniques and treatment interventions have had obvious impact on outcomes in cutaneous melanoma, but the effects on outcome in MMHN remain undefined. This study aims to assess the outcome and identify clinical and histologic prognostic indicators in a recent cohort of patients with MMHN treated at a single institution. METHODS: The clinical records of 59 patients with the diagnosis of MMHN treated at Memorial Sloan-Kettering Cancer Center (MSKCC) between 1978 and 1998 were retrospectively reviewed. Pathologic material on each of these patients was prospectively reviewed by at least two pathologists (MP, KB, or AH) for confirmation of diagnosis and assessment of histologic variables. Survival was calculated by the Kaplan-Meier method. Clinical (patient demographics, tumor characteristics, and treatment) and histologic data (tumor thickness, melanosis, melanoma in situ, vascular invasion, and multifocality) were analyzed for impact on outcome by both univariate and multivariate analyses. RESULTS: Thirty-five patients (59%) had sinonasal tumors (SNMM), whereas 24 (41%) had oral (ORMM) tumors. Forty-seven patients (79.6%) were staged as stage I, 8 (13.6%) as stage II, and 4 (6.8%) were classified as stage III. Regional lymphatic metastases at presentation were more frequent in ORMM compared with SNMM (25% vs 6%, p =.05). Surgery was used in all patients. Adjuvant radiation therapy was used more frequently in the SNMM group compared with the ORMM group (40% vs 17%, p =.04). The rates of local failure for ORMM and SNMM were 51% and 50%, nodal failure rates were 42% and 20%, and distant failure rates were 67% and 40%, respectively (p = NS). With a median follow-up of 20 months, the 5-year disease-specific survival rate was 44% (40% for ORMM vs 47% for SNMM, p = NS). Significant prognostic factors for disease-specific survival on univariate analysis included advanced clinical stage at presentation, tumor thickness greater than 5 mm, presence of vascular invasion, and development of nodal and distant metastases. On multivariate analysis, however, regional nodal failure lost significance. CONCLUSIONS: Clinical stage at presentation, tumor thickness greater than 5 mm, vascular invasion on histologic studies, and development of distant failure are the only independent predictors of outcome in MMHN.