The Symptoms of Varicose Veins: Difficult to Determine and Difficult to Study

ObjectivesTo investigate the activities which may exacerbate symptoms in patients with varicose veins.MethodsQuestionnaires sent to patients before clinics and at least six months later.ResultsBoth questionnaires were returned by 149 of 203 patients (74%) but only 124 contained adequate data for comparison – 55 from patients who had surgical treatment and 69 who had no surgery. At initial presentation, worsening of discomfort attributed to varicose veins was common during (58%) or after (48%) standing and in hot weather (44%), but less when sitting with the feet down (31%), and after (31%) or when walking (19%). Surgery significantly reduced the total number of symptoms reported by patients at follow-up (p<0.02). However, none of the symptoms reported during specific activities was significantly lessened by surgery compared with no treatment – possibly because the attrition of patients during the study resulted in small numbers for analysis.ConclusionsSymptoms are a common indication for treating varicose veins and it is therefore important to be sure that they are due to the veins, rather than other causes. This report highlights traditional and logical questions which may help to identify symptoms caused by varicose veins but illustrates the difficulty of validating them

Vitamin D supplementation in cutaneous malignant melanoma outcome (ViDMe): a randomized controlled trial.

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Spontaneous life-threatening hemobilia during acute liver failure successfully treated with transarterial embolization

A 28-year-old patient admitted with jaundice, vomiting and deteriorating coagulopathy was diagnosed with acute liver failure. After listing for urgent transplantation, he developed Boerhaave’s syndrome and massive hemobilia, two life-threatening complications. Massive hemobilia secondary to a fistula between the right hepatic artery and the right bile duct occurred several days after transjugular biopsy and was controlled with fluid resuscitation, transfusion and arterial embolization. Two days later he was transplanted successfully, and is currently doing well after more than 72 months. Aggressive treatment of potentially reversible complications during acute liver failure whilst awaiting transplantation is mandatory to allow survival of these patients

The effects of itopride on oesophageal motility and lower oesophageal sphincter function in man

BACKGROUND: Itopride is a new prokinetic agent that combines antidopaminergic and cholinesterase inhibitory actions. Previous studies suggested that itopride improves heartburn in functional dyspepsia, and decreases oesophageal acid exposure in gastro-oesophageal reflux disease. It remains unclear whether this effect is due to effects of itopride on the lower oesophageal sphincter (LES). AIMS: To study the effects of itopride on fasting and postprandial LES function in healthy subjects. METHODS: Twelve healthy volunteers (five men; 32.6 ± 2.0 years) underwent three oesophageal sleeve manometry studies after 3 days premedication with itopride 50 mg, itopride 100 mg or placebo t.d.s. Drug was administered after 30 min and a standardized meal was administered after 90 min, with measurements continuing to 120 min postprandially. Throughout the study, 10 wet swallows were administered at 30-min intervals, and gastrointestinal symptoms were scored on 100 mm visual analogue scales at 15-min intervals. RESULTS: Lower oesophageal sphincter resting pressures, swallow-induced relaxations and the amplitude or duration of peristaltic contractions were not altered by both doses of itopride, at all time points. Itopride pre-treatment inhibited the meal-induced rise of transient LES relaxations (TLESRs). CONCLUSIONS: Itopride inhibits TLESRs without significantly affecting oesophageal peristaltic function or LES pressure. These observations support further studies with itopride in gastro-oesophageal reflux disease

Effect of rimonabant on oesophageal motor function in man

BACKGROUND: Cannabinoid type 1 (CB1) receptors are implicated in the control of transient lower oesophageal sphincter relaxations (TLESRs) in animals. In man, it is unclear whether CB1 receptors are involved in the control of oesophageal function. AIM: To study the effects of the CB1 receptor antagonist rimonabant on fasting and postprandial LES function in healthy subjects. METHODS: Twelve healthy volunteers underwent two oesophageal manometry studies with administration of wet swallows and a meal after 3 days' premedication with placebo or rimonabant 20 mg. RESULTS: Rimonabant did not significantly alter preprandial LES pressure (21.1\ub14.0 vs. 17.3\ub13.0 mmHg, N.S.), but postprandial LES pressures were significantly enhanced (9.9\ub11.9 vs.17.1\ub12.7 mmHg in the first and 10.0\ub11.4 vs. 19.3\ub13.6 mmHg in the second postprandial hour, both P<0.05). Swallow-induced relaxations and amplitude of peristaltic contractions were not altered, but rimonabant significantly increased the duration of peristaltic contractions at all time points (e.g. 5.0\ub10.3 vs. 8.0\ub10.3s preprandially and 5.0\ub10.2 vs. 8.2\ub10.3s at 60 min postprandially, both P<0.01). The number of postprandial TLESRs (3.1\ub10.5 vs. 1.2\ub10.5, P<0.05) and acid reflux episodes (1.4\ub10.2 vs. 0.3\ub10.1, P<0.05) were significantly lower after rimonabant. CONCLUSION: The CB1 receptor antagonist rimonabant enhances postprandial LES pressure and decreases TLESRs in healthy subjects

Vitamin D supplementation in cutaneous malignant melanoma outcome (ViDMe) : a randomized controlled trial

Background: Previous studies have investigated the protective effect of vitamin D serum levels, at diagnosis and during the follow-up period after treatment, on melanoma outcome. In the present study we assess whether vitamin D supplementation, in the follow-up period after diagnosis and surgical resection of the primary tumor, has a protective effect on relapse of cutaneous malignant melanoma and whether this protective effect correlates with vitamin D levels in serum and Vitamin D Receptor immunoreactivity in the primary tumor. Methods/design: This study is a multicenter randomized double blind placebo- controlled phase III trial. Patients between the age of 18 and 80years diagnosed and treated surgically for a melanoma stage IB-III are eligible for randomization in a 1:1 ratio to active treatment or placebo. The study drug is taken each month and consists of either 100,000 International Unit cholecalciferol or arachidis oleum raffinatum used as a placebo. The primary endpoint is relapse free survival. The secondary endpoints are 25 hydroxyvitamin D3 serum levels at diagnosis and at 6month intervals, melanoma subtype, melanoma site and stage of melanoma at diagnosis according to the 2009 American Joint Committee on Cancer melanoma staging and classification. At randomization a bloodsample is taken for DNA analysis. The study is approved by the local Ethics Committees. Discussion: If we can confirm our hypothesis that vitamin D supplementation after removal of the tumor has a protective effect on relapse of cutaneous malignant melanoma we may reduce the burden of CMM at several levels. Patients, diagnosed with melanoma may have a better clinical outcome and improved quality of life. There will be a decrease in health care costs related to treatment of metastatic disease and there will be a decrease in loss of professional years, which will markedly reduce the economic burden of the disease. Trial registration: Clinical Trial.gov, NCT01748448 , 05/12/2012 © 2017 The Author(s)

Road to Metastasis: The TWEAK Pathway as a Discriminant between Metastasizing and Non-Metastasizing Thick Melanomas

Cutaneous melanoma (CM) is the most aggressive form of skin cancer, and its worldwide incidence is rapidly increasing. Early stages can be successfully treated by surgery, but once metastasis has occurred, the prognosis is poor. However, some 5–10% of thick (≥2 mm) melanomas do not follow this scenario and run an unpredictable course. Little is known about the factors that contribute to metastasis in some patient with thick melanomas and the lack thereof in thick melanoma patients who never develop metastatic disease. We were therefore interested to study differential gene expression and pathway analysis and compare non-metastatic and metastatic thick melanomas. We found that the TNF-like weak inducer of apoptosis (TWEAK) pathway was upregulated in thick non-metastasizing melanomas. MAP3K14 (NIK1), BIRC2 (cIAP1), RIPK1, CASP7, CASP8, and TNF play an important role in inhibiting proliferation and invasion of tumor cells via the activation of the non-canonical NF-κB signaling pathway. In particular, this pathway sensitizes melanoma cells to TNF-alpha and activates the apoptosis module of the TWEAK pathway in thick non-metastasizing melanomas. Hence, our study suggests a potential role of the TWEAK pathway in inhibiting thick melanoma from metastasis. Exploitation of these genes and the pathway they control may open future therapeutic avenues