No abstract

Hereditary Haemorrhagic Telangiectasia (HHT) or Rendu-Osler-Weber syndrome, is an autosomal dominant rare disease characterized by localized angiodysplasia. This is manifested as epistaxis, mucocutaneous and gastrointestinal telangiectases, and arteriovenous malformations in the pulmonary, cerebral or hepatic circulation. The prevalence is between 1 in 5,000 to 8,000, although it is higher in some regions. The most frequent clinical manifestation of HHT is epistaxis, normally from light to moderate from the 4(th) decade of life. However, many patients show severe epistaxis which may interfere with their quality of life. The epistaxis is due to telangiectasia on the nasal mucosa. These are focally dilated postcapilar venules, which in advanced phases show many layers of smooth muscle cells without elastic fibers, and very frequently directly connect with dilated arterioles. As a consequence of these vascular alterations, telangiectases are very sensitive to slight trauma and even to the friction with the air when breathing, which gives rise to nose bleeds. Unfortunately, there is no optimal pharmacological treatment for the epistaxis in HHT. The use of antifibrinolytic agents for the treatment of HHT has been studied recently by our group as an effective relief for nasal and gastric haemorrhages. This work represents a systematic review and the beginning of a systematic laboratory work we are now conducting in our lab to screen for "orphan drugs" as therapeutic agents in HHT. In this context, the use of hormones, immunosuppresants and anti-angiogenic agents are under preclinical study in our laboratory.

Aim: To describe epidemiological characteristics of a wide cohort of Spanish patients with hereditary hemorrhagic telangiectasia (HHT)/ Rendu-Osler-Weber disease. Methods and Results: Between 1 January 2002 and 31 December 2013, 667 Spanish patients with suspected HHT were evaluated in the reference HHT Unit in Hospital Sierrallana and 449 were diagnosed by clinical Curaçao criteria and/or genetic test. The diagnostic sensitivity of Curaçao clinical criteria in the population studied was 94.59%. Prevalence was 1:5,936 people and lethality rate of 0.16%. Type 2 HHT was the most prevalent and in total 147 different mutations was identified. Epistaxis was the most prevalent symptom (96.88% of cases) while 95.18% of patients showed typical telangiectasias. Pulmonary involvement was present in 28.25% of patients (by computed tomography) mainly in women and HHT1 cases while liver infection was more prevalent in HHT2 cases. Brain involvement was disclosed in 28.35% of cases. Telangiectasias in conjuctival mucose were very frequent mainly in HHT1 elderly patients. Conclusion: This is the first representative series of epidemiological data on a non-previously evaluated population, showing results about prevalence, genetic distribution and organ infection and disclosing new observations that can help guide the diagnostic and screening procedures for these patients.

No abstract

Although miniDOX's toxicity (mainly PE)has been important, its activity has been promising in "suboptimal" pts with AGC, and this combination should be further investigated in this setting.

87 Background: Chemotherapy has improved overall survival (OS) in patients (p) with AGC and docetaxel (D), oxaliplatin (O) and capecitabine (X), have shown consistent activity in this setting. We defined "Suboptimal" p as those with PS ECOG-2 and/or weight loss 10-25% and/or age ≥70 years. This population is usually underrepresented in AGC clinical trials. Methods: We explored in 43 previously untreated "suboptimal" AGC p the "miniDOX" regimen (D: 40 mg/m2 iv, d1; O: 80 mg/m2 iv d1; C: 625 mg/m2 po bid, d1 to 21, every 21d; after 6 courses only C was maintained). D and O dose were allowed to be increased to 45 and 90 mg/m2 respectively (dose level +1) and to 50 and 100 mg/m2 (level +2) if less than grade 2 toxicity after the first 2 courses. One p that did not received any dose of chemotherapy, was included in the ITT efficacy analysis but not in the safety analysis. Primary endpoint was Response Rate (RR), Toxicity, Progression Free Survival (PFS) and OS were secondary objectives. Results: p characteristics: PS ECOG-2:12 p, Weigh loss 10-25%:23 p; median age 73.3 years (40-87); 32 males; locally advanced:8 p/metastatic:35 p; Primary site:Gastric 32 p/ EGJ 11; In 19 p the dose of D and O were increased to level +1 and in 8 of them to level +2. Worst toxicity per p (Grade 3-4): neutropenia: 5 p (3 of them with febrile neutropenia); pulmonary embolism (PE):4 p (3 of them suffered sudden death and the PE was suspected but not confirmed); diarrhea:9 p; paronychia:2 p; CVA:1 p; renal failure:1 p (this p suffered infection/bacteriemia without neutropenia and died); hand-foot syndrome:4 p and asthenia:5 p. Response: CR:1 p, PR:23 p (RR: 56%), SD:12 p, Progression:3 p, No determined:4 p; With a median follow-up of 27 months, 36 p have died (toxicity:4 p, progressive disease:32 p). Median and 1 year actuarial PFS and OS are 5.5 months/19% and 13.3 months/54% respectively. Conclusions: Although relevant the toxicity of miniDOX has been found, its activity is encouraging in "suboptimal" pts with AGC and this combination should be further investigated in this setting. Clinical trial information: NCT00733616.

were made at 48 and 96 h according to the ICDRG (International Contact Dermatitis Research Group) guidelines. The results are shown in Table 1. The positive reactions to wool alcohols, fragrance mix, colophony, and balsam of Peru had past relevance, but the positive reaction to black rubber mix did not. Six weeks later, we retested the patient with PG (0.5%, 1% and 2% aq.) showing positive results at D2 with PG 1% and 2% aq. We also performed a ROAT (repeated open application test) with PG 2% aq. (two applications per day) in the antecubital fossa. After 2 days, an eczematous reaction appeared on the treated area. Funk & Maibach classify skin reactions to PG into four mechanisms: irritant contact dermatitis, allergic contact dermatitis, nonimmunologic contact urticaria, and subjective or sensory irritation (2). The distinction between irritant and allergic reactions associated with PG application remains unclear. Furthermore, the irritation threshold of PG and the optimal standard concentration in patch tests are not well established. Usually a PG concentration of 1±10% aq. is recommended for patch tests in order to avoid irritation (2, 3). However, some authors recommend raising the standard PG concentration in patch tests to 20% and in doubtful cases even higher (50%) (4, 5). True allergic sensitization to PG should be con®rmed by repeated patch testing, serial dilutions, usage tests/ROAT, or oral challenge tests (in certain cases). Data on the incidence 2. Funk JO, Maibach HI. PG dermatitis:re-evaluation of an old problem. Contact

R0 resections after IC and before RT could indicate an improvement in OS in patients with T4b-SCHNC that obtain less than a 90% PR at primary after IC. We consider that this approach deserves further research in prospective clinical trials.