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Calcifying pseudoneoplasm of the neuroaxis (CAPNON) is a rare, slow growing, and generally benign fibro osseous mass that can emerge throughout the entire central nervous system (CNS). When diagnosed, prompt surgical treatment can determine a good neurological outcome and possibly curative resolution. The objective of the present work is to present a step by step technical report with its video. We present a 37 year old female presented with occipital headache and cervical pain associated with dysphagia, nausea, and gait disturbances. Computed tomography (CT) scan showed a focal calcified lesion on the floor of the IV ventricle projecting toward the vermis with associated supratentorial hydrocephalus and transependymal edema. The telovelar approach was chosen for the procedure. The outcome was favorable, with no complications. Postoperative CT was performed, which revealed no residual lesion. A step by step report of a IV ventricle CAPNON that manifested with hydrocephalus is described.

Summary Background In European countries, suboptimal intake has been reported for several micronutrients (as calcium, iron, zinc, vitamin B12, D and folate) in both adulthood and childhood. No studies to date have prospectively compiled nutrient intake from healthy children in different European countries using the same methodology. Aim To describe the adequacy of micronutrient intake during the first eight years of life in children from 5 European countries. Methods Prospective observational trial analyzing data from the EU Childhood Obesity Project. Infants were enrolled within the first two months of life and were followed regularly to age 8 years. Dietary intake was collected periodically with 3-day food records. Nutrient intake adequacy was estimated for calcium, phosphorus, iron, zinc, magnesium, iodine, folate and vitamins B12, A and D, following the American Institute of Medicine (IOM) guidelines at group (prevalence of adequacy >80%) and individual (high probability of adequate intake >80% of the children) level; the assessment was based on the Estimated Average Requirements of nutrients of the FAO, WHO and United Nations University (FAO/WHO/UNU) or the IOM if FAO/WHO/UNU data were not available. Results Intake data were available for a decreasing number of children, from 904 at 3 months to 396 at 8 years. Iron, iodine, folate and vitamin D were inadequately consumed when assessing adequacy at group level; at individual-level less than 80% of the children showed high probability of adequate intake for iron, iodine, folate and zinc at all ages, and calcium from 12 months onwards. Conclusions Accurate dietary intake and adequacy assessment methodology in this prospective cohort of European children found iron, calcium, vitamin D, folate, iodine and zinc to be inadequately consumed in childhood, as described previously by epidemiologic studies. Further studies are needed to elucidate health consequences of these deficiencies. CHOP trial was registered at clinicaltrials.gov as NCT00338689 .

Background and aims The double-blind randomized European Childhood Obesity Project (CHOP) demonstrated that reduced protein content in infant formula leads to a lower body mass index (BMI) up to six years of age. Here we aimed at assessing pre-peritoneal fat, a marker of visceral fat, in children participating in the CHOP trial. Methods and results Healthy term formula-fed infants in five European countries were randomized either to higher (n = 550) or lower (n = 540) protein formulas in the first year of life. Infants who were exclusively breastfed for at least three months (n = 588) were enrolled as an observational (non randomized) group. At age 5 years, subcutaneous fat (SC) and pre-peritoneal fat (PP) were measured by ultrasound in a subgroup of 275 children. The PP fat layer was thicker in the higher compared to the lower protein group (adjusted estimated difference: 0.058 cm, 95%CI 0.002; 0.115; p = 0.043), while SC fat was not different. Girls showed a thicker SC fat layer than boys. Conclusions Higher protein intake in formula-fed infants appears to enhance pre-peritoneal fat tissue accumulation at the age of 5 years, but not of subcutaneous fat, which may trigger adverse metabolic and health consequences.

IF 7.191 (2017); International audience; BACKGROUND:Previous studies showed that high and low body mass index (BMI) was associated with worse prognosis in early-stage colorectal cancer (CRC), and low BMI was associated with worse prognosis in metastatic CRC (mCRC). We aimed to assess efficacy outcomes according to BMI.PATIENTS AND METHODS:A pooled analysis of individual data from 2085 patients enrolled in eight FFCD first-line mCRC trials from 1991 to 2013 was performed. Comparisons were made according to the BMI cut-off: Obese (BMI ≥30), overweight patients (BMI ≥ 25), normal BMI patients (BMI: 18.5-24) and thin patients (BMI

Background Serum IgE evaluation of peanut, hazelnut and walnut allergens through the use of component-resolved diagnosis (CRD) can be more accurate than IgE against whole food to associate with severe or mild reactions. Objectives The aim of the study was to retrospectively define the level of reaction risk in children with peanut, hazelnut and walnut sensitization through the use of CRD. Methods 34 patients [n = 22 males, 65%; median age eight years, interquartile range (IQR) 5.0–11.0 years] with a reported history of reactions to peanut and/or hazelnut and/or walnut had their serum analyzed for specific IgE (s-IgE) by ImmunoCAP® and ISAC® microarray technique. Results In children with previous reactions to peanut, the positivity of Arah1 and Arah2 s-IgE was associated with a history of anaphylaxis to such food, while the positivity of Arah8 s-IgE were associated with mild reactions. Regarding hazelnut, the presence of positive Cora9 and, particularly, Cora14 s-IgE was associated with a history of anaphylaxis, while positive Cora1.0401 s-IgE were associated with mild reactions. Concerning walnut, the presence of positive Jug r 1, Jug r 2, Jug r 3 s-IgE was associated with a history of anaphylaxis to such food. ImmmunoCAP® proved to be more useful in retrospectively defining the risk of hazelnut anaphylaxis, because of the possibility of measuring Cor a14 s-IgE. Conclusions Our data show that the use of CRD in patients with allergy to peanut, hazelnut and walnut could allow for greater accuracy in retrospectively defining the risk of anaphylactic reaction to such foods.

Background and aims No data exist in the current literature on the glycemic index (GI) and glycemic load (GL) of the diet of phenylketonuric (PKU) children. The aims of this study were to examine the dietary GI and GL in PKU children on a low-phenylalanine (Phe)-diet and to evaluate whether an association may exist between the carbohydrate quality and the metabolic profile. Methods Twenty-one PKU children (age 5–11 years) and 21 healthy children, gender and age matched, were enrolled. Dietary (including GI and GL) and blood biochemical assessments were performed. Results No difference was observed for daily energy intake between PKU and healthy children. Compared to healthy controls, PKU children consumed less protein ( p = 0.001) and fat ( p = 0.028), and more carbohydrate (% of total energy, p = 0.004) and fiber ( p = 0.009). PKU children had higher daily GI than healthy children (mean difference (95% confidence interval), 13.7 (9.3–18.3)) and higher GL (31.7 (10.1–53.2)). PKU children exhibited lower blood total and low density lipoprotein cholesterol (LDL) levels ( p p = 0.014) than healthy children, while glucose and insulin concentrations did not differ. In PKU children the dietary GL was associated with triglyceride glucose index (Spearman's correlation coefficient = 0.515, p = 0.034). Conclusion In PKU children a relationship of the dietary treatment with GI and GL, blood triglycerides and triglyceride glucose index may exist. Improvement towards an optimal diet for PKU children could include additional attention to the management of dietary carbohydrate quality.

Background Sorafenib is an oral anticancer agent targeting Ras-dependent signaling and angiogenic pathways. A phase I trial demonstrated that the combination of gemcitabine and sorafenib was well tolerated and had activity in advanced pancreatic cancer (APC) patients. The BAYPAN study was a multicentric, placebo-controlled, double-blind, randomized phase III trial comparing gemcitabine/sorafenib and gemcitabine/placebo in the treatment of APC. Patients and methods The patient eligibility criteria were locally advanced or metastatic pancreatic adenocarcinoma, no prior therapy for advanced disease and a performance status of zero to two. The primary end point was progression-free survival (PFS). The patients received gemcitabine 1000 mg/m2 i.v., weekly seven times followed by 1 rest week, then weekly three times every 4 weeks plus sorafenib 200 mg or placebo, two tablets p.o., twice daily continuously. Results Between December 2006 and September 2009, 104 patients were enrolled on the study (52 pts in each arm) and 102 patients were treated. The median and the 6-month PFS were 5.7 months and 48% for gemcitabine/placebo and 3.8 months and 33% for gemcitabine/sorafenib (P = 0.902, stratified log-rank test), respectively. The median overall survivals were 9.2 and 8 months, respectively (P = 0.231, log-rank test). The overall response rates were similar (19 and 23%, respectively). Conclusion The addition of sorafenib to gemcitabine does not improve PFS in APC patients.

http://hdl.handle.net/20.500.11768/96439 Background: During the period that randomized clinical trials were establishing the role of adjuvant therapy in tumors larger than 5 cm without lymph-node invasion, which shifted from stage IB (6th TNM) to stage II (7th TNM), we derived the rate of shifted patients in our series and analyzed the relationship between specific patient- and tumor-characteristics, and clinical outcome, to identify putative prognostic factors. Methods: We retrospectively collected data (age, sex, smoking status, type of surgery grading, and histological type) from 467 patients who underwent radical surgery for primary 6th TNM-T2N0 non-small cell lung cancer patients between 1998 and 2009 at our institute. Categorical variables were cross-tabulated by tumor staging according to the 7th TNM edition, and they were tested both for association with stage and survival. Results: One hundred and eighteen patients shifted to stage II, mainly older patients and patients with a sarcomatoid or a poorly differentiated carcinoma. Median overall survival time was significantly different across stages. Among the factors investigated, only the tumor dimension resulted in being statistically significant in multivariate analysis. Conclusions: Nearly a quarter of patients shifted from stage I (6th TNM) to stage II (7th TNM), raising a major need for information on the effects of adjuvant chemotherapy in this group of patients. Our findings suggest that randomized clinical trials aimed at addressing this topic should consider only tumor dimensions as principal selection criteria.

Introduction Mutations of the epidermal growth factor receptor (EGFR) have been proven to predict activity of the EGFR-tyrosine kinase inhibitors (EGFR-TKI), gefitinib and erlotinib. Although the "common" EGFR mutations, such as the L858R point mutation in exon 21 and the in-frame deletional mutation in exon 19, have been definitively associated with response to EGFR-TKIs, the correlation with response to treatment for many other rarer mutations is still unclear. In this study, we report the results of treating patients with advanced non-small cell lung cancer harboring rare EGFR mutations treated with EGFR-TKIs. Methods The frequency of rare mutations has been investigated in 681 cases of non-small cell lung cancer screened between 2006 and 2010. Mutations in exons 18 and 20, uncommon mutations in exons 19 and 21, and/or the presence of different mutations in a single tumor (complex mutations) were considered rare. Results EGFR mutations were detected in 99 tumors (14.5%). Eighteen cases carried rare mutations, and 10 of these patients were treated with erlotinib or gefitinib. The clinical outcome was described case by case with references to the literature. Of note, we found two EGFR mutations never identified before and one of unknown response to EGFR-TKIs. Conclusions Gefitinib and erlotinib have different antitumor activity according to the type of the EGFR mutation borne. Report of cases harboring rare mutations can support the decision-making process in this subset of patients.

Summary The number of patients with uncontrolled asthma is growing especially in young people. Although current therapies improve the disease management, the heterogeneity of clinical outcomes results in patients whose asthma is refractory to standard therapies. To understand not responsive phenotypes, we instituted a web-registry aimed to collect real life data of adolescent and adult patients. One-hundred and five Italian medical Centers are part of the network. Participants above 14 years and affected by severe asthma will be included in the study. Demographic and clinical data will be collected for 5 years on a dedicated electronic database. For the first time in Italy, our study will provide information on epidemiological, clinical and therapeutic aspects related to the natural course of the disease, filling the gap between adolescents and adults.

Background Pancreatic endocrine tumors (PETs) differ in clinical behavior and prognosis. Determination of malignant potential through specimens obtained by EUS-FNA can help in the management of these patients. Objective To determine the value of EUS-FNA for diagnosing PETs and for classifying their underlying malignant potential based on the World Health Organization (WHO) classification. Design Single-center, retrospective, cohort study. Setting Tertiary referral hospital. Patients This study involved 86 consecutive patients (44 men, mean age 58 ± 14 years) who had been diagnosed with PETs and submitted to EUS-FNA from January 1999 to August 2008. Intervention EUS-FNA of a pancreatic mass and/or a metastasis site. Immunohistochemistry on microbiopsies or on monolayer cytology was routinely used. The lesions were classified as recommended by the WHO. Main Outcome Measurements EUS-FNA sensitivity and 5-year survival rate. Results Overall, in 90% (77 of 86) of patients in this study, PET was diagnosed with EUS-FNA. The sensitivity did not vary with tumor size, type, location, or the presence of hormonal secretion. Of 86 patients, 30 (35%) were submitted to surgical resection. The kappa correlation index between the WHO classification obtained by EUS-FNA and by surgery was 0.38 ( P = .003). Major discrepancies were found in the group of patients diagnosed with endocrine tumor of uncertain behavior by EUS-FNA, because 72% turned out to have well-differentiated endocrine carcinoma. Sixteen patients (27%) died during a mean follow-up period of 34 ± 27 months. The 5-year survival rates were 100% for endocrine tumors, 68% for well-differentiated endocrine carcinomas, and 30% for poorly differentiated endocrine carcinomas ( P = .008, log-rank test). Limitations Retrospective design, selection bias, and small sample size. Conclusions This largest single-center experience to date demonstrated the accuracy of EUS-FNA in diagnosing and determining the malignant behavior of PETs. EUS-FNA findings predict 5-year survival in patients with PETs.

This dose escalation study was designed to determine the maximum tolerated dose (MTD) and recommended doses (RDs) of 5-fluorouracil (5FU), folinic acid and oxaliplatin (FOLFOX) with concomitant radiotherapy in inoperable/metastatic oesophageal squamous cell carcinoma or adenocarcinoma. Patients received three courses of LV5FU2 regimen (folinic acid 200 mg m(-2), bolus 5FU 300-400 mg/m(2), continuous infusion 5FU 400-600 mg m(-2) on days 1 and 2) and escalating doses of oxaliplatin 50 to 100 mg m(-2) on day 1 (FOLFOX). This regimen was repeated every 2 weeks, concomitant to a 50-gray radiotherapy per 5 weeks. Three more cycles were delivered after completion of radiation therapy. Three to six patients were allocated to each of the five dose levels until MTD was reached. Thirty-three patients were enroled and 21 had metastatic disease. Maximum tolerated dose was oxaliplatin 100 mg m(-2), and continuous infusion 5FU was 600 mg m(-2) day(-) (level 5). The most common toxicities were neutropenia, dysphagia and oesophagitis. The RDs were those of FOLFOX-4 regimen (oxaliplatin 85 mg m(-2) and full doses of LV5FU2). The overall response was 48.5%, including 12% complete response. Response rate on primary tumour was 62.9%. This FOLFOX-4 regimen was reasonably well tolerated and effective in inoperable/metastatic oesophageal carcinoma and warrants additional investigation.

Background and study aims Endoscopic retrograde cholangiopancreatography (ERCP) access to the biliary tract is sometimes impossible and percutaneous access has the disadvantages of increased morbidity and patient discomfort. We present our first results with an alternative technique: endoscopic ultrasonography (EUS)-guided transgastric biliary drainage. Patients and methods 11 patients (7 men, mean age 64 years) were referred for failed ERCP and biliary obstruction (malignancy n = 8, benign conditions n = 3). The retrograde approach via the papilla had been impossible due to surgical anatomy, duodenal stenosis, and hilar stricture with occlusion of the left side. EUS-guided drainage was done with endoscopic and fluoroscopic monitoring. After puncture of the left biliary duct a guide wire was inserted into it followed by tract dilation using a cystostome. A plastic or a metallic stent was placed through this gastrobiliary fistula for bile drainage. Results EUS-guided left hepaticogastrostomy was successfully performed in 10/11 cases, with one failure of guide wire insertion after puncture. Plastic and covered metal stents were inserted in seven and three patients, respectively. Complications in the plastic stent group included one early occlusion requiring stent replacement, and one transient ileus. In the metallic stent group there was one bilioma and one cholangitis, due to stent shortening. Clinically, the stent was efficacious in all 10 cases; during a mean follow-up of 213 days (range 3-610), two patients presented with stent occlusion and one with stent migration, with successful endoscopic treatment in all. Conclusions EUS-guided hepaticogastrostomy is an efficient technique and could be a future alternative to percutaneous biliary drainage or palliative surgical drainage.

Barrett’s esophagus–related high-grade dysplasia or mucosal cancer can be treated by endoscopic mucosal resection (EMR), but the adjacent metaplastic epithelium remains at risk for developing further lesions. Our objective was to evaluate the results of the circumferential EMR in removing not only the neoplastic lesion but also the remaining Barrett’s epithelium. Forty-one consecutive patients (mean age: 66 years) with Barrett’s esophagus were submitted to 63 EMR sessions in one single-referral endoscopic unit. All patients had high-grade dysplasia, and cancer was detected in 23 of these cases, most of them classified as T1N0 (20 patients) by endosonography. Mucosectomy after saline submucosal injection was performed for the neoplastic lesions and, if necessary, the residual Barrett’s epithelium was removed by the same technique one month later. A retrospective evaluation showed that, during a mean follow-up of 31.6 months, Barrett’s epithelium was completely replaced by squamous epithelium in 31 (75.6%) cases. There were 10 complications, all of which were managed endoscopically: 8 cases of bleeding and two perforations occurred in 9 (14.3%) patients. One patient developed an esophageal stricture. Barrett’s epithelium recurred in 10 (24.4%) patients and recurrent or metachronous early cancer was detected in 5 (12.2%), all but one of which were treated again by EMR; the fifth patient was referred to surgery. Argon plasma coagulation was used in 6 cases to treat Barrett’s epithelium, and two patients received concomitant chemoradiotherapy as adjuvant therapy. Circumferential EMR provides an effective endoscopic approach to the management of Barrett’s esophagus-related high-grade dysplasia and mucosal cancer. Additional studies are necessary to evaluate the long-term results.

Background and study aims The aim of this study was to evaluate the efficacy and outcomes of treatment by endoscopic mucosal resection (EMR) of patients with high-grade dysplasia (HGD) or carcinoma. Patients and methods Between January 1995 and January 2002, 50 patients (35 men, 15 women) were treated by EMR for 52 sessile polyps. The median size of the polyps was 27.5 mm (range 10-60). The "lift and cut" EMR technique was used. If the lesion was poorly differentiated or infiltrated the muscularis mucosae to more than 1000 microm, the patient was referred for colectomy. In the other cases, follow-up was proposed. Results Complications occurred in 9.6 % of cases and were always treated conservatively. The rate of endoscopically complete resection was judged to be 98.1 %. Argon plasma coagulation was applied to the margins of the lesion in 21.6 % of cases. Histological examination showed 38 HGDs and 14 carcinomas. Seven patients had a lesion reaching the deep or lateral margin; four were referred for surgery; two patients for whom surgery would have been high risk were followed up, and both developed local recurrence; and one patient was followed up, without recurrence, because infiltration was less than 1000 microm. A total of 43 patients were followed up after complete excision. Two patients died during follow-up; neither death could be reliably attributed to colorectal carcinoma. Seven patients were lost during the follow-up. For 34 patients, information from a mean follow-up of 17.3 months (6 - 57) was available and recurrence was observed in five cases (15 %). Conclusions EMR appears to be a safe and efficient treatment of HGD and early colorectal cancer. However, correct analysis of submucosal infiltration is essential to assess the completeness of the resection.

Summary Overall prognosis of adenocarcinomas of the gastro-esophageal junction remains poor as most patients present with advanced disease. Aim To examine the effects of preoperative chemoradiotherapy in locally advanced adenocarcinomas of the gastro-esophageal junction. Methods Forty-two consecutive patients received a course of radiotherapy (45 Gy, administred in 25 fractions) with concurrent infusion of 5-fluorouracil and cisplatin, followed by surgery. Endoscopic ultrasonography was used to assess response to chemoradiotherapy. A transhiatal or a transthoracic approach was used for surgical resection. Tumor size, node invasion and margins of resection were analyzed. Results Thirty-eight patients underwent subsequent surgery and complete resection (R0) was achieved in 34. Operative mortality was 13.2% (5/38). A histological complete response was observed in 6 patients. Median survival was 23 months (range: 15-31) and median disease-free survival was 19 months (range: 15-23). At one and two years, 70.7 and 45.6% of the patients were alive, respectively. The pTNM status, node involvement and tumor size were predictors of survival. Conclusions Pre-operative chemoradiotherapy is effective in patients with locally advanced carcinoma of the gastro-esophageal junction, resulting in high resection rates. However it seems to increase operative morbidity and mortality. Certain prognostic factors such as resection margins, need to be examined in further detail.

Environmental contaminants such as persistent organic chlorines and heavy metals, which are supplied to the foetus by transplacental transfer and to breastfed infants by the milk, may impair cognitive functions. Long-chain polyunsaturated fatty acids, which are known to enhance development during foetal life and early infancy, may counteract the toxic effect of environmental contaminants. In this study, we have investigated whether polychlorinated biphenyls (PCBs) impair early development of vision, and whether such impairment can be modulated by essential long-chain polyunsaturated fatty acids.Healthy term infants born in Milan and its surroundings, and who were exclusively breastfed for at least 4 mo, were prospectively examined up to the age of 12 mo.Samples from colostrums, the first 2 d after delivery, and of mature breast-milk after 1 and 3 mo were collected. The samples were analyzed for PCB 105, 118, 138, 153, 156 and 180 and for DDT and DDE. In all infants, the plasma levels of the long-chain polyunsaturated fatty acids (LC-PUFAs), C18:2 n-6, C18:3 n-3, C20:4 n-6, C20:5 n-3 and C22:6 n-3 were analysed within the first three postnatal days. The PCB levels in colostral milk, as well as of LC-PUFAs in plasma, were considered to mirror perinatal supply. Visual function was evaluated by P100 with latency evoked potentials (VEPs) at 12 mo of age. Statistical analysis was based on simple and partial correlation coefficients (p0.05).On bivariate analysis, wave latency VEP at 15 min was significantly related to the colostral levels of DDT, DDE and all examined PCBs except PCB 105 (with correlation coefficient r = 0.401 to 0.618), whereas P100 wave latency VEP at 60 min was related to DDT (r = 0.513) and PCB 180 (r = 0.504). Infant plasma levels of C22:6 n-3 were inversely associated with P100 wave latency at 60 min (r = -0.418) and at 1Hz-2J (r = -0.466). After controlling for C22:6 n-3, the partial correlation coefficient of P100 wave latency VEP at 15 min to the colostral level of PCB 180 was 0.403 (p = 0.07).Within the population of this study, a weak relation was found between impaired visual function at 12 mo of age of healthy infants and the levels of PCBs, DDT and DDE in colostral milk. The effect of impairment was no longer evident after controlling for the plasma level of LC-PUFAs as found in the infant a few days after birth.

Laminin is a basement membrane glycoprotein implicated in a large number of biologic activities of cancer progression, many of which are mediated by the presence of the laminin receptor (67LR) on the cell membrane. We studied the correlations of laminin and its receptor with standardized and new prognostic factors (including bone marrow micrometastases) in a series of 112 patients with operable breast cancers. Laminin-positive cells were detected in 60% of the tumors and 67LR-positive cells in 55%; both were present in 35% of the cases. No association was found between laminin or 67LR positivity and pathologic tumor size, pathologic nodal status, grading, Ki-67, estrogen receptor status, progesterone receptor status, or bone marrow micrometastases. The only statistically significant association was with menopausal status and age, with a higher percentage of 67LR-positive tumors among premenopausal and younger patients. The median follow-up was approximately 7 years. The prognosis of disease-free survival was similar in the laminin-positive and laminin-negative subjects but was significantly better in 67LR-negative patients; there were no significant differences in overall survival. The prognostic role of laminin and 67LR in disease-free survival and overall survival varied according to nodal status. In the absence of nodal involvement, the risk of relapse (and death) was greater in the patients who were positive for laminin, 67LR, or both than in those who were negative for laminin, 67LR, or both; in the case of 4 or more involved nodes, the prognostic role of laminin and 67LR was reversed. These results did not change after adjustment for age, menopausal status, tumor status, nodal status, grading, or bone marrow micrometastases.

Objective: To investigate the relation between maternal smoking habits, plasma lipids and milk fatty acid (FA) content and composition. Design: Breastfeeding mothers who gave birth to healthy, full-term infants were recruited. Mothers were interviewed on smoking habits, being defined smokers (S) when usually smoking at least five cigarettes per day before pregnancy. Setting: Department of Pediatrics, San Paolo Hospital, Milan, Italy. Subjects: In total, 92 mothers: 61 non-S (NS) and 31 S. Interventions: Pooled hindmilk was collected at the first raise of milk (colostrum stage), 1, 3 and 6 months, and total lipid (TL) content and fatty acid (FA) composition were evaluated. Maternal dietary habits were assessed by a food-frequency questionnaire. Two subsamples (16 NS, 6 S) were investigated after delivery and at 3 months for serum lipids and FA status. At 6 months after delivery, the number of mothers still breastfeeding decreased to 30. Variables were compared using nonparametric tests. Results: In smoking mothers serum levels of triglycerides, cholesterol and low-density lipoproteins were higher, while those of high-density lipoproteins were lower. TL content in breast milk was similar in the two groups just after delivery but higher in milk from NS at 1 month. TL content and FA absolute amounts of linoleic, arachidonic, α-linolenic and docosahexaenoic (DHA) acid in breast milk were lower in S vs NS 1 month after delivery. Also 3 months after delivery, the breast milk of smoking mothers contained less DHA than the breast milk of nonsmoking mothers. Conclusions: Maternal cigarette smoking in early pregnancy is associated with higher plasma lipid levels and lower milk TL and DHA content in the first months of lactation.

But de l'Etude: Recemment l'echoendoscopie (EE) a ete utilisee pour drainer des pseudokystes ou des abces pancreatiques. Le but de ce travail a ete d'utiliser l'EE comme moyen de drainage de collections pelviennes peri-rectales en general postoperatoire, en utilisant un echoendoscope interventionnel a gros canal operateur. Patients et Methodes: De septembre 2000 a juin 2001,12 patients (9 hommes, 3 femmes) d'âge moyen 67 ans (extremes: 48-77 ans) ont presente une collection abcedee pelvienne peri-rectale et ont eu une tentative de traitement guidee par EE. Il s'agissait 10 fois d'abces retro-rectaux apres resection anterieure du rectum pour cancer,1 fois d'une collection suppuree du cul de sac de Douglas apres hysterectomie pour cancer du col de l'uterus, et 1 fois d'un abces peri-sigmoidien compliquant une sigmoidite diverticulaire chez un patient presentant une leucemie aigue en phase d'induction therapeutique (aplasie profonde). Le drainage de ces collections etait realise sous un triple controle-endoscopique, radiologique et echoendoscopique. L'appareil utilisee permettait l'utilisation de materiel de 8.5 F de diametre. La technique consistait a reperer dans un premier temps la cavite abcedee et d'en realiser la ponction avec une aiguille de 19 gauges permettant de recueillir du pus pour etude bacteriologique. Un lavage soigneux de la cavite par du serum sale etait alors realise jusqu'a obtention d'un liquide clair. Dans un second temps, une injection de contraste permettait de bien delimiter l'abces. Celui-ci rempli de serum physiologique etait alors ponctionne avec un infundibutome de 5.5 F, permettant l'introduction d'un fil guide de 0.035 et la mise en place sur ce fil guide d'une prothese de 8.5 F afin d'assurer un drainage endo-luminal. Resultats: Aucune complication n'est survenue, ni perforation, ni hemorragie. Une prothese trans-rectale a pu etre mise en place 9 fois sur 12 et dans 3 cas une simple aspiration-lavage a ete realisee. Parmi ces 3 cas, 2 ont recidive tres rapidement et ont du etre reoperes. Parmi les 9 patients chez qui une prothese trans-rectale avait pu etre inseree, la collection suppuree a disparu completement 8 fois sur 9. La prothese trans-rectale a ete laisse en place en moyenne 4.3 mois et a ete retiree endoscopiquement sans complication. Conclusion: 11 s'agit donc d'une technique prometteuse permettant d'eviter une deuxieme intervention dans environ 80% des cas.

Purpose: To study the efficacy and safety of percutaneous cisplatin-epinephrine (CDDP-EPI) injectable gel in patients with localized unresectable hepatocellular carcinoma (HCC). Patients and Methods: Eligible patients had histologically proven HCC, no prior treatment except for surgery, and no more than three tumors (each measured ≤ 7 cm, total tumor volume ≤ 200 cm3). They were treated percutaneously under ultrasound or computed tomography (CT) guidance, with up to 10 mL of CDDP-EPI gel (1 mL contains 4 mg of CDDP and 0.1 mg of EPI) per treatment and four treatments in 6 weeks to a maximum of eight treatments. The primary end points were tumor response, defined by change of percentage of tumor necrosis according to CT criteria, and safety. Survival parameters were secondary end points. Results: From June 1997 to April 2000, 58 patients (median age, 65 years) entered the study. All patients were assessable for safety, and 51 were assessable for efficacy. The median number of treatments was four (range, one to eight treatments). Objective response rate was 53% (27 of 51 patients), including 16 complete and 11 partial responses. Of the 27 responders, 14 (52%) subsequently developed progressive disease, but in most of them (93%), a new tumor arose at untreated liver sites. Median survival was 27 months (range, 18.4 to 35.7 months). The 1-, 2-, and 3-year survival rates were 79%, 56%, and 14% respectively. The procedure was well tolerated with only minor side effects. Conclusion: Percutaneous local ablation with CDDP-EPI injectable gel can induce significant tumor necrosis and local control for localized unresectable HCC, and the treatment is well tolerated.

Proliferative activity has been proposed as a prognostic and predictive marker for breast cancer; Ki-67 is one of the most frequently used markers to assess proliferative activity. In the current study, Ki-67 immunoreactivity was comparatively assessed, even in terms prognostic relevance, with 3H-thymidine labeling index as a reference standard for proliferation in 126 patients with stage I and II breast cancer. There was a significant but weak correlation between Ki-67 values and the 3H-thymidine labeling index (r = 0.19, P = 0.03). Analysis of variance showed that the mean 3H-thymidine labeling index values were not statistically different in terms of pathologic size (T1, T2. T3, T4), number of pathologically positive axillary nodes (neg, pos 1-3, pos > 3), and grading classes (1, 2, 3), but significantly and inversely correlated with estrogen receptor status (P = 0.033) and progesterone receptor status (P = 0.08). The Ki-67 values significantly correlated with N status (P = 0.041), estrogen receptor status (P < 0.001), progesterone receptor status (P < 0.001), and grading (P < 0.001). The median follow-up was 37 months. In terms of prognosis, Ki-67 was associated significantly with overall survival (P = 0.01) and marginally with disease-free survival (P = 0.095). A significant difference in prognosis was found for both disease-free survival (P = 0.024) and overall survival (P = 0.040) when a 3H-thymidine labeling index cut-off of 6.5% was used (P = 0.024). The results suggest that, although both are indicators of proliferative activity, 3H-thymidine labeling index and Ki-67 seem to identify breast cancers with different phenotypes.

Significance Meteorologists and geoscientists have called for greater consideration of social science factors that predict responses to natural hazards. We answer this call by highlighting the influence of an unexplored social factor, gender-based expectations, on the human toll of hurricanes that are assigned gendered names. Feminine-named hurricanes (vs. masculine-named hurricanes) cause significantly more deaths, apparently because they lead to lower perceived risk and consequently less preparedness. Using names such as Eloise or Charlie for referencing hurricanes has been thought by meteorologists to enhance the clarity and recall of storm information. We show that this practice also taps into well-developed and widely held gender stereotypes, with potentially deadly consequences. Implications are discussed for understanding and shaping human responses to natural hazard warnings.

Usually, hyperresponsiveness to inhaled methacholine is considered closely associated with a diagnosis of bronchial asthma. Recently, it has been clearly pointed out that bronchial hyperreactivity (BHR) is not a constant feature of asthma and that this condition is not always related to airways inflammation. In the present study we evaluated 42 Patients (21 positive and 21 negative for bronchial hyperreactivity, BHR) with the aim to determine the effect of Methacholine Challenge Testing (MCT) on the levels of exhaled nitric oxide (NO). Higher FeNO levels were found before methacholine provocation in the group that eventually resulted positive to the challenge, while after the challenge in both groups FeNO decreased in similar way, with no statistical difference. These data confirm that MCT is a relevant test for asthma diagnosis, but it is not always related to the severity of bronchial inflammation, while FeNO levels in our study have limited clinical significance when evaluated out of asthma exacerbation.

Buts de l'Etude: La classification des cancers du canal anal repose sur l'examen clinique et l'appreciation de la hauteur tumorale (Classification UICC 1987). Cette classification a une application therapeutique directe puisque les tumeurs classees T1 et T2 sont generalement traitees par une radiotherapie exclusive et les lesions classees T3, T4 ou N+ quelque soit le T relevent d'une radiochimiotherapie. Le but de ce travail prospectif multicentrique a ete d'evaluer l'EEAR et de definir une classification us TN pronostique. Patients et Methodes: De janvier 1994 a mai 1997, 146 patients (42 hommes et 104 femmes d'âge moyen 63 ans) ont ete inclus dans cette etude par huit differents centres. La classification us TN apprecie le degre d'infiltration parietale et l'extension ganglionnaire perirectale basse et haute (charniere) mais ignore l'atteinte ganglionnaire inguinale: tumeur usT1, atteinte de la muqueuse et sous-muqueuse sans infiltration du sphincter interne; tumeur usT2, atteinte du sphincter interne avec respect du sphincter externe; tumeur usT3, atteinte du sphincter externe; tumeur usT4, atteinte d'un organe pelvien de voisinage; N0, pas d'adenopathie suspecte perirectale; N+, adenopathie(s) perirectale(s) ayant des criteres echoendoscopiques de ganglion malin (rond, hypoechogene, contours nets). Les tumeurs classees UICC T1 et T2 ( 4 cm), T3 et T4, N0-N1-2-3 ont beneficie d'une radiochimiotherapie concomitante. Resultats: Les donnees concernant la reponse au traitement et le suivi des patients (septembre 1997) ont ete disponible chez 115/146 patients inclus (78.7%). Nous avons compare l'impact pronostic des deux classifications sur la reponse au traitement et sur la survenue d'une recidive locoregionale (test chi-deux). Pour la reponse au traitement, 56/70 UICC T1-T2N0 (80%) ont eu une reponse complete, contre 34/36 usTl-2N0 (94.5%; P=0.008); par contre le N evalue aussi bien cliniquement que par EEAR n'est pas pronostic. Pour le diagnostic de recidive, le T et le N evalues cliniquement n'est pronostique (respectivement P = 0.4 et P= 0.5); par contre usT et usN sont hautement predictif (respectivement P = 0.001 et P = 0.03), Conclusion: Les resultats preliminaires de cette etude multicentrique prospective montrent que le us T est predictif de la reponse au traitement et que usT et usN sont predictifs d'une recidive locoregionale. L'etude devra etre poursuivie pour apprecier le caractere pronostique de l'EEAR sur la survie.

Background and Study Aims: The aim of this study was to evaluate the efficacy of endoscopic mucosectomy (EM), and to present our experience with the endoscopic removal of superficial tumors of the gastrointestinal tract. Patients and Methods: A total of 21 patients were included in the study (16 men, 5 women), between September 1995 and May 1997. In 16 cases the site of the lesions was an esophageal carcinoma, in two cases a gastric carcinoma, and in three cases a sessile polyp of the duodenum with severe dysplasia. Surgery was not recommended for the patients with esophageal or gastric tumors (on account of cardiac disease, cirrhosis or poor health). All patients underwent an endoscopic ultrasound (EUS) examination. The lesions were classified as usT1N0 in 20 cases, and usT0N0 in one case, according to the pretreatment EUS findings. We used the technique of polypectomy after submucosal injection of 10-15 ml of saline serum. Results: Complications were encountered in 2/21 patients (9.5 %). Bleeding occurred in one case, but hemostasis was achieved endoscopically. In the other case, the patient presented with a thoracic pain and was treated by morphine injection. Endoscopic resection was considered to be complete in 19/21 patients (90.4%). In the other two cases, both involving esophageal tumors, histologic examination indicated only a partial tumor removal. However, these two patients had survived with negative EUS and endoscopic biopsy findings at 18 and 22 months later, respectively. None of the patients whose resections were considered complete presented with local recurrence, but three patients developed another superficial esophageal cancer, which was also treated by endoscopic mucosal resection (EMR). The mean follow-up was 20 months. Conclusions: EMR is a safe and efficient treatment of early gastrointestinal tumors. The development of high-frequency EUS probes may further improve the results of this technique in the future.

Studies have been underway since 1981 on the scapular anatomic unit as a new donor site for reconstructive surgery. Anatomic studies have proven that this diaphyseal bone has a large osteocartilaginous growth epiphysis at its inferior pole, which is responsible for development of 80% of the surface of the scapula. Experimental investigations and clinical studies have revealed minimal functional limitation because of loss of the scapular crest and that its growth plate can be used beneficially for vascularized bone transfer. Four cases are reported with good results based on 2 to 14 years followup without significant impairment of the donor site.

The potent serotonin receptor (5-HT3) antagonists are new highly selective agents for the prevention and control of chemotherapy-induced nausea and vomiting that have been shown to be comparable to or more effective than traditional metoclopramide regimens. This study was designed to compare the antiemetic efficacy of dolasetron and metoclopramide in chemotherapy-naive and non-naive cancer patients receiving high-dose cisplatin-containing chemotherapy. This multicentre, double-blind, randomized trial compared the efficacy and safety of single i.v. doses of dolasetron mesilate salt (1.2 or 1.8 mg/kg) and metoclopramide (7 mg/kg) in 226 patients for the prevention of acute emesis and nausea associated with the administration of high-dose (or = 80 mg/m2) cisplatin. Efficacy and safety were evaluated for 24 h. Complete responses were achieved by 57%, 48%, and 35% of patients given dolasetron mesilate 1.8 mg/kg (P = 0.0009 vs metoclopramide), dolasetron mesilate 1.2 mg/kg (P = 0.0058 vs metoclopramide), and metoclopramide, respectively. Overall, dolasetron was significantly more effective than metoclopramide for time to first emetic episode, nausea, patient satisfaction, and investigator global assessment of efficacy. Males, chemotherapy-naive patients, and alcoholics had higher response rates. Dolasetron was well tolerated, with mild-to-moderate headache most commonly reported. Twelve percent of patients receiving metoclopramide reported extrapyramidal symptoms compared with 0% of patients receiving dolasetron. In conclusion, dolasetron mesilate was effective for the prevention of CINV with high-dose cisplatin. Single i.v. doses of dolasetron mesilate were more effective than 7 mg/kg metoclopramide in preventing nausea and vomiting induced by highly emetogenic cisplatin-containing chemotherapy. In addition, 1.8 mg/kg dolasetron mesilate consistently produced the highest response rates and appears to be the most effective dose for further clinical development.

A comparison of 692 early invasive breast cancer with, and 1564 without, a family history of breast cancer showed that the former were younger at diagnosis (P=0.002), had smaller tumours (P=0.012), were more frequently oestrogen receptor positive (P=0.006) and diagnosed preclinically (P

PURPOSE To compare the efficacy and toxicity profiles of a combination of fluorouracil (5-FU) with recombinant human interferon alfa-2a (Roferon-A; Hoffman La-Roche AG, Basel, Switzerland) versus the combination of 5-FU with leucovorin (LV) in the treatment of advanced colorectal cancer. PATIENTS AND METHODS A total of 496 previously untreated colorectal cancer patients were randomized to receive either Roferon-A (9 MIU) subcutaneously three times per week, with 5-FU (750 mg/m2/d) by continuous intravenous (i.v.) infusion (CIV) on days 1 to 5, then, after a 9-day hiatus, as a weekly i.v. bolus at the same dose (IFN/5-FU); or LV (200 mg/m2/d) by i.v. infusion plus 5-FU (370 mg/m2/d) by i.v. bolus on days 1 to 5, repeated every 4 weeks (LV/5-FU). RESULTS There were no significant differences between IFN/5-FU and LV/5-FU in the overall response rate (21% v 18%), duration of response (7.3 v 6.2 months), or survival time (median, 11.0 v 11.3 months). Toxicity profiles differed; constitutional symptoms and myelosuppression were more frequent and more severe with IFN/5-FU, and gastrointestinal symptoms with LV/5-FU. More patients interrupted treatment for adverse events (AEs) with IFN/5-FU than with LV/5-FU. Five treatment-related deaths occurred with each regimen. CONCLUSION The combination IFN/5-FU produced response rates, response durations, and survival times similar to those with LV/5-FU. Biochemical modulation of 5-FU by either IFN or LV appears to result in equivalent efficacy; however, fewer patients were able to tolerate the specified IFN/5-FU combination used in this study.

The results of the neonatal screening for phenylalanine hydroxylase (PAH) deficiency in Sicily show that its incidence is higher than previously reported for mainland Italians and that non-PKU HPA is in excess of classical and mild PKU. The latter finding suggests that a high number of non-PKU HPA mutations would occur in the Sicilian population compared to populations with an inverted PKU/non-PKU HPA ratio. Previous studies have identified 40 mutations accounting for the majority (98%) of mutant alleles underlying PAH deficiency in Sicily. In order to study the molecular basis of the distribution of PAH deficiency phenotypes in the Sicilian population, we have correlated 31 of those mutations with clinical and metabolic phenotypes in 12 mentally retarded patients, 14 treated patients with classic or mild PKU, and 13 subjects presenting the non-PKU HPA phenotype. The present study proposes a tentative classification for a large number (26) of PAH gene mutations which may represent an additional tool for establishing a differential diagnosis for PAH deficiency in the Sicilian population.

β-thalassaemia major (TM) is an inherited disorder of erythropoiesis requiring regular blood transfusions and chelation therapy for the iron overload resulting from transfusions and increased gastrointestinal absorption. Endocrine dysfunctions are common in older children with TM and has been attributed to iron deposition in endocrine glands. The Authors report the clinical and histological findings of endocrine glands in a prepubertal girl with multiple endocrine complications secondary to iron overloadn died from cardiac failure. Variations in severity of the disease and therapeutic regimens may result in different incidence and types of complications It is emphasized the importance of chelating therapy to protect endocrine glands from haemosiderosis.

Confocal endomicroscopy is an emergent technique and allows real optical biopsies in the gastrointestinal (GI) tract. The aim of this study was to evaluate a new intraductal confocal miniprobe in patients with a normal common bile duct (CBD) or with a suspicion of a malignant stenosis (cholangiocarcinoma).Thirty-seven patients (23 males) underwent endoscopic retrograde cholangiopancreatography (ERCP) for bile duct stone removal (7 cases) or bile duct stenosis (30 cases). Intraductal confocal microscopy (IDCM) was performed during the ERCP using a probe-based confocal laser endomicroscopy (pCLE) technique. IDCM was done with the CholangioFlex probe with Cellvizio (Mauna Kea Technologies, Paris, France). The depth of penetration of theCholangioFlex probe was 40-70 μm and magnification was 400×. Images were reviewed by an experienced pathologist in GI disease and compared to ERCP findings, CBD biopsies performed during ERCP or EUS, and in 15 patients to the resected specimen (Wipple resection).No complications related to the CholangioFlex insertion occurred after the ERCP. Good images were obtained in 33 patients. Final histology diagnosis was a normal CBD in 7 cases, 23 malignant stenoses (4 ampullary carcinomas, 13 cholangiocarcinomas, and 6 pancreatic cancer), and 7 inflammatory stenoses (4 chronic pancreatitis, 1 stenosis of hepaticojejunal anastomosis, 1 postcholecystectomy CBD stenosis, and 1 primary sclerosing cholangitis). IDCM of a normal CBD showed a thin black band (20 μm), normal vessels (thin and regular), and no visible glands. IDCM of malignant strictures revealed irregular vessels with lack of contrast in the CBD wall, large black band (20 μm), and an aggregate of irregular black cells (black clumps). These aspects were seen in all malignant stenoses and none were seen in benign or normal CBD. The presence of irregular vessels, large black bands, and black clumps seen with confocal laser microscopy enabled prediction of neoplasia with an accuracy rate of 86%, sensitivity of 83%, and specificity of 75%. The respective numbers for standard histopathology were 53, 65, and 53%.This phase I-II study on IDCM showed that IDCM is feasible. This new technique will open a new door for optical biopsy of the CBD.

To evaluate whether a relationship exists in hospital admissions for respiratory conditions in children with outdoor pollution in the Southwest Milan, Italy.Daily count of hospital admissions for asthma, upper or lower respiratory diseases (LRD) occurred among children agedor =14 years at the San Paolo Hospital during 2007-2008 was recorded. Pollutants included the particular matter of10 microm diameter, ozone, carbon monoxide (CO) and nitrogen dioxide (NO(2)), reported on the same day of admission and 1 up to 5 days before admission. The moving weekly average (MWA) was also considered.Total respiratory admissions were associated with the same day level of CO (30.6% increase per 1 mg/m(3) increase, 95% confidence interval, 3.9-69.9%) and with the MWA of NO(2) (9.0% increase per 10 microg/m(3) increase, 1.2-16.8%). The effect of CO was stronger on upper respiratory diseases (URD) (lag 0, 21.3% increase, 6.4-38.3%). The effect of NO(2) was stronger on LRD (MWA, 5.3% increase, 0.9-10.2%). Multipollutant models confirmed the role of CO on URD and that of NO(2) on LRD.Carbon monoxide and nitrogen dioxide may be associated with emergency hospital admissions for respiratory conditions among children in Southwest Milan.

Neoadjuvant chemoradiation followed by surgery is the standard of care for locally advanced rectal cancer. The aim of this study was to correlate tumour response to survival and to identify predictive factors for tumour response after chemoradiation.From 1998 to 2008, 168 patients with histologically-proven locally advanced adenocarcinoma treated by preoperative chemoradiation before total mesorectal excision were retrospectively studied. They received a radiation dose of 45 Gy with a concomitant 5-fluoro-uracil-based chemotherapy. Analysis of tumour response was based on the lowering of T stage between pre-treatment endorectal ultrasound and pathologic specimens. Overall and progression-free survival was correlated with tumour response. Tumour response was analysed with predictive factors.The median follow-up was 34 months. Five-year disease-free survival and overall survival were respectively of 44.4% and 74.5% in the whole population, 83.4% and 83.4% in patients with pathological complete response, 38.6% and 71.9% in patients with tumour downstaging, 29.1% and 58.9% in patients with absence of response. A pre-treatment concentration of carcinoembryonnic antigen below 5 ng/mL was significantly associated with tumour downstaging and significantly independently associated with pathologic complete tumour response (P = 0.019).Downstaging and complete response after chemoradiation improved progression-free survival and overall survival of locally advanced rectal adenocarcinoma. In multivariate analysis, a pre-treatment concentration of carcinoembryonnic antigen below 5 ng/mL was associated with complete tumour response, hence with tumour downstaging.

A study was carried out in five children with acquired immune deficiency syndrome to assess the effect of combined zidovudine/interferon-α2a therapy with that of zidovudine given alone on immunological profiles and plasma zidovudine concentrations. Immunoglobulins A, G and M, total and absolute CD4 lymphocyte counts, and p24 antigen concentrations did not differ significantly when children were treated with 300 mg/m2 zidovudine given orally once every 12 h, or with 150 mg/m2 zidovudine plus 1.5 or 3 MIU interferon-α2a given intramuscularly three times weekly. Peak plasma zidovudine concentrations were significantly ( P < 0.05) lower when combined treatment with 150 mg/m2 zidovudine/1.5 MIU interferon-α2a was administered compared with 300 mg/m2 zidovudine alone, or combined 150 mg/m2 zidovudine/3 MIU interferon-α2a The results suggest that combination zidovudine/interferon-α2a therapy may be more efficacious than zidovudine alone and that the normal zidovudine dose may be reduced if interferon-α2a is given in addition, thus reducing the side-effects associated with zidovudine.

As clarithromycin (CLA), an antibiotic commonly used for Helicobacter pylori eradication, stimulates gastroduodenal motility, we investigated whether it also stimulates esophageal motility. In 15 normal subjects, esophageal motility was recorded using a low-compliance manometric system with two ports in the esophageal body, one port in the lower esophageal sphincter (LES), and five ports in the antroduodenal tract to monitor the occurrence of phases I-III of the migrating motor complex. Thirty minutes after the occurrence of a duodenal phase III, we infused intravenously, randomly, and in a double-blind manner, CLA 100 mg in five subjects (group A), CLA 250 mg in five subjects (group B), and normal saline in the remaining five subjects (group C). LES tone and post-deglutitive residual pressure, as well as the amplitude and duration of the esophageal contractions, were measured each minute and averaged over a post-infusion period of 30 min. Both group A and B showed a LES tone significantly higher than that of group C after CLA infusion, whereas the post-deglutitive residual pressure was not significantly different from that of group C. The LES tone of group B was significantly higher than that of group A. Group B, but not group A, showed a wave amplitude and duration significantly higher than that of group C. In conclusion, CLA is able to stimulate LES tone and esophageal contractions with a dose-related effect.

The aim of the study was to explore the illness experience of individuals affected by phenylketonuria (PKU) and its differences in different patient age groups.A qualitative-interpretative methodology was used through in-depth interviews. Textual data were explored using the principles of grounded theory.Forty-seven patients participated in the study, aged from 10 to25 years old. The results suggested the age-related PKU experience: (1) a paradox, either to feel normal but isolated from the social context, or to be different while participating in the convivial aspects of the social being; and (2) the need for education about the disease tailored to the individual and growing needs. Specific themes seem to characterize each age range.This study constitutes a first attempt at understanding PKU from a non-medical-biological perspective.

Angiogenesis is considered one of the key mechanisms of tumour growth and survival. Therefore it represents an ideal pharmaceutical target. Many antiangiogenic agents have been developed so far in several solid tumours and also in breast cancer. Vascular endothelial growth factor (VEFG) is the main target and both monoclonal antibodies and small molecules belonging to the tyrosine kinase inhibitors directed against VEGF(R) have been developed. Some other therapeutic approaches have shown to exert some antiangiogenic activity, such as hormonal agents, metronomic chemotherapy, bisphosphonates and others. In this paper we provide an introduction of the current data supporting the angiogenesis in breast cancer and a review of the most relevant antiagiogenic therapies which have been investigated so far.

Carnitine has a fundamental biological role as a long-chain fatty acid carrier across the mitochondrial membrane and in ketone body formation. Although the body normally synthesizes carnitine, in certain circumstances such as total parenteral nutrition and haemodialysis a dietary supplement may be needed to maintain adequate levels. Several considerations suggest that carnitine is a truly essential nutrient in infancy and in other situations where the energy requirement is particularly high, e.g. pregnancy and breast feeding. There are, for example, congenital deficit syndromes due to enzymatic inadequacies. There is also the possible role of carnitine in serious metabolic disorders such as organic acidaemias and, above all, it has multiple physiological functions in major metabolic pathways which are essential for development and growth.

Hemolytic uremic syndrome (HUS) in children is classically associated with diarrheas related to the production of a shiga-toxin. HUS occurs among oncologic patients, in relation with the cancer itself, or as a complication of the cytostatic treatment. The physician should be familiar with the triad of HUS (microangiopathic hemolytic anemia, thrombocytopenia and renal failure) and search actively for this pathology in oncologic patient. The treatment is essentially empirical. It includes plasma exchanges, control of blood pressure, hydro-electrolytic balance control with dialysis, if necessary. Blood transfusion should be avoided. Potential mortal complications associated with HUS can be prevented by a rapid diagnosis and a prompt initiation of adequate therapy.

To describe the longitudinal pattern of dietary energy and macronutrient intakes during the first 10 years of life in a sample of healthy Italian children.Sixty-one healthy children were followed from birth to 10 years of age. At 1, 5, 8, and 10 years of age, anthropometric measurements were taken and nutritional habits evaluated using a standardized food frequency questionnaire.Compared to the Italian recommended dietary allowances, the children's diet was high in protein at any age, high in lipids from age 5 onward, and high in calories at 5 years of age. At 1 year, mean (SD) protein, carbohydrate, and lipid intake, expressed as percentage of total energy, was 20% (3%), 48% (7%), and 34% (5%), respectively. Afterward, the corresponding mean value ranged around 14% to 15%, 57% to 60%, and 29% to 32%. The mean glycemic load and overall glycemic index ranged around 143 to 150 and 58 to 59, respectively. A difference between boys and girls was found in the longitudinal pattern for the intake of energy (P0.0001) and glycemic load (P0.0001). The individual longitudinal dietary pattern varied over time for the intake of total energy (P0.0001), any macronutrient (P0.0001), and overall glycemic index (P = 0.05).Although the amount of energy intake was in accordance with the Italian recommended dietary allowances, children consumed a high-protein and high-lipid diet. Early and continuous dietary education of children and parents may provide support for adequate nutritional habits throughout their childhood.

Background and Study Aims: It is well known that some diseases, such as cancer, lead to changes in the hardness of tissue. Sonoelastography, a technique that allows the elasticity of tissue to be assessed during ultrasound examination, provides the ultrasonographer with important additional information that can be used for diagnosis. The aim of this study was to evaluate the ability of endoscopic ultrasound elastography to differentiate between benign and malignant pancreatic masses and lymph nodes.Patients and Methods: During a 12-month period, 49 patients underwent endoscopic ultrasound (EUS) examinations with elastography, conducted by a single endoscopist. Twenty-four patients underwent evaluation of a pancreatic mass (mean diameter 24.7 ± 11.1mm) and 25 underwent evaluation of 31 lymph nodes. The mean diameter of the lymph nodes was 19.7 ± 8.6 mm, and they were found in the cervical area (n = 3), mediastinum (n = 17), celiac arterial trunk region (n = 5), and aortocaval region (n = 6).Results: The sonoelastography images of pancreatic masses were interpreted as benign in four cases and malignant in 20. The sensitivity and specificity of sonoelastography in the diagnosis of malignant lesions were 100 % and 67 %, respectively. The sonoelastography images of the lymph nodes were interpreted as showing malignancy in 22 cases, benign conditions in seven, and indeterminate status in two. The sensitivity and specificity of sonoelastography for evaluating malignant lymph-node invasion were 100 % and 50 %, respectively.Conclusions: EUS elastography is potentially capable of further defining the tissue characteristics of benign and malignant lesions but specifity has to be improved. It can be used to guide biopsy sampling for diagnosis.

Background and Study Aims: Using EUS in the study of portal hypertensive patients, various divisions of the gastroesophageal collateral circulation can be demonstrated. The azygos vein, which is the main drainage system for varices, can also be scanned endosonographically. We studied the azygos vein in control subjects and portal hypertensive patients using EUS. Patients and Methods: Our study included 17 patients with endoscopic evidence of esophagogastric varices and 11 control subjects not suffering from chronic liver disease or varices. EUS and Doppler EUS using a linear scanning echoendoscope were carried out on patients and control subjects with the aim of studying the azygos vein. Results: The azygos vein could be scanned in all subjects and was found to be significantly dilated in patients with varices. Maximal velocity of its blood flow was higher among patients with varices compared to control subjects. Periazygos collaterals could be occasionally observed in portal hypertensive patients. Conclusion: EUS can be used both for scanning and hemodynamic studies of the azygos vein. The fact that EUS allows the collection of valuable quantitative and qualitative data from the azygos vein should encourage further studies on the clinical value of this information in the follow up of portal hypertensive patients.

Background Obstructive sleep apnoea has been demonstrated to induce gastrooesophageal reflux through highly negative intrathoracic pressure during the attacks. However, we believe that gastrooesophageal reflux on its part may favour or aggravate the apnoea attacks. Aims We investigated whether the treatment of gastrooesophageal reflux with omeprazole is able to decrease apnoea attacks. Patients and methods Twenty patients (mean age 55.4 years, range 49–73 years; 17 males) with confirmed obstructive sleep apnoea at overnight polysomnography and pathological gastrooesophageal reflux at ambulatory 24-h oesophageal pHmetry were asked to note in a diary the occurrence of apnoea attacks for a basal period of 4 weeks. Subsequently, the patients were randomly and in a double-blind manner treated with omeprazole 20 mg (10 patients, group A) or placebo (10 patients, group B) by giving 1 cp 30 min before breakfast and 1 cp 30 min before dinner for another 6 weeks with a diary documentation. The results were averaged weekly and over the entire treatment duration and a statistical comparison was made between the groups and within each group before and after treatment. Results The mean weekly frequency of apnoea attacks of group A during the entire period of treatment with omeprazole was significantly decreased with respect to the basal period and was significantly lower than that of group B. The weekly frequency of apnoea attacks in group A started to be significantly lower from the third week than the corresponding values of both group B and the basal period, reaching a decrease of about 73% in the sixth week. Conclusion The occurrence of apnoea attacks progressively decreased during the treatment of gastrooesophageal reflux with omeprazole. This fact suggests that gastrooesophageal reflux may play a role in triggering and/or worsening obstructive sleep apnoea.

Drug treatment and specific immunotherapy (SIT) are both effective in seasonal rhinoconjunctivitis, but the former acts only on allergic symptoms while the latter modifies the natural history of the disease. Only a few studies compared the clinical efficacy of the two treatments with contrasting results. We planned a study to compare the efficacy of SIT (15 patients) and drug treatment (15 patients) in moderate to severe seasonal rhinoconjunctivitis caused by sensitization to grass pollen. SIT was performed by a 5-grass extract standardized in IR and absorbed onto calcium phosphate (Phostal, Stallergénes, Antony, France) using the conventional build-up phase in 12 weeks and a maintenance treatment with monthly injection for three years. Drug treatment was done with cetirizine as antihistamine, mometasone furoate as nasal topical steroid, and levocabastine eyedrops. All patients registered during the pollen season their symptoms and drug consumption. After one year 12 of 15 patients treated with SIT had less symptoms and drug consumption in respect to baseline compared to none in drug treated group (p = 0.021) and after three years 15 of 15 were improved in group A compared to one of 15 in group B (p = 0.008). These findings indicate an higher efficacy of SIT in patients with seasonal rhinitis not only in the long term but also in the first year of treatment.

Assessing impact of major liver resection (LR) for hepatic metastasis of colorectal cancer (HMCC) on post operative courses and long term survival in the elderly.Thirty-three consecutive patients aged over 70 years-old were treated in our institution for up to 3 resectable metachronous HMCC. Fifteen patients had major LR (9 right hepatectomy, 3 extended right hepatectomy, 3 left hepatectomy) without pre or postoperative chemotherapy (group 1) and 18 patients were exclusively treated by chemotherapy (group 2) because of high ASA score (ASA 3) or patients refusal.No patients died of another cause that colorectal cancer disease during observation time. All patients of group 2 died during observation time. Post operative mortality and morbidity of group 1 were respectively 0% and 33%. Survival at 1 and 2 years of group 1-2 were respectively 73-50% (P=0,04) and 47-15% (P=0,05). Median survival of group 1 and 2 were respectively 22 and 12 months (P=0,03).Major LR for HMCC could be proposed regardless the age. High ASA score, multiple (more than 4) metastasis location, evolutive disease could justify an exclusive medical approach.