Dr Josep Trueta Hospital

Girona, Spain

Dr Josep Trueta Hospital

Girona, Spain
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Figueras J.,Dr Josep Trueta Hospital | Sabater L.,University of Valencia | Planellas P.,Dr Josep Trueta Hospital | Munoz-Forner E.,University of Valencia | And 6 more authors.
British Journal of Surgery | Year: 2013

Background Anastomotic leakage of pancreaticojejunostomy (PJ) remains the single most important source of morbidity after pancreaticoduodenectomy (PD). The primary aim of this randomized clinical trial comparing PG with PJ after PD was to test the hypothesis that invaginated PG would result in a lower rate and severity of pancreatic fistula. Methods Patients undergoing PD were randomized to receive either a duct-to-duct PJ or a double-layer invaginated PG. The primary endpoint was the rate of pancreatic fistula, using the definition of the International Study Group on Pancreatic Fistula. Secondary endpoints were the evaluation of severe abdominal complications (Clavien-Dindo grade IIIa or above), endocrine and exocrine function. Results Of 123 patients randomized, 58 underwent PJ and 65 had PG. The incidence of pancreatic fistula was significantly higher following PJ than for PG (20 of 58 versus 10 of 65 respectively; P = 0·014), as was the severity of pancreatic fistula (grade A: 2 versus 5 per cent; grade B-C: 33 versus 11 per cent; P = 0·006). The hospital readmission rate for complications was significantly lower after PG (6 versus 24 per cent; P = 0·005), weight loss was lower (P = 0·025) and exocrine function better (P = 0·022). Conclusion The rate and severity of pancreatic fistula was significantly lower with this PG technique compared with that following PJ. Registration number: ISRCTN58328599 (http://www.controlled-trials.com). This pancreaticogastrostomy technique is superior © 2013 British Journal of Surgery Society Ltd. Published by John Wiley & Sons Ltd.

Ibanez L.,University of Barcelona | Ibanez L.,Institute Salud Carlos III | Lopez-Bermejo A.,Dr Josep Trueta Hospital | Diaz M.,University of Barcelona | And 4 more authors.
Journal of Clinical Endocrinology and Metabolism | Year: 2011

Context: Girls with a combined history of low(-normal) birth weight (LBW) and precocious pubarche (PP) are at high risk to develop polycystic ovary syndrome (PCOS). Objective: The objective of the study was to compare the capacity of early vs. late metformin treatment to prevent adolescent PCOS. Design: This was a randomized, open-label study over 7 yr. Setting: The study was conducted at a university hospital. Patients: Thirty-eight LBW-PP girls were followed up from the mean age 8 until age 15 yr. Intervention: Early metformin (study yr 1-4; age 8-12 yr) vs. late metformin (yr 6; age 13-14 yr). Main Outcome Measures: Measures included height; weight; hirsutism score; menstrual cycle; endocrine-metabolic screening (fasting; follicular phase); C-reactive protein; body composition (absorptiometry); abdominal fat partitioning (magnetic resonance imaging); ovarian morphology (ultrasound); PCOS (National Institutes of Health and Androgen Excess Society definitions) after yr 7 (all girls thus untreated for at least 1 yr). Results: None of the girls dropped out of the study. At age 15 yr, early-metformin girls were taller (4 cm), were in a less proinflammatory state, and had less central fat due to reductions in visceral and hepatic fat. Hirsutism, androgen excess, oligomenorrhea, and PCOS were between 2- and 8-fold more prevalent in late- than early-treated girls. Abdominal adiposity was the first variable to diverge (at age 8-10 yr) between girls without vs. with PCOS at age 15 yr. Conclusions: In LBW-PP girls, early metformin therapy was found to prevent or delay the development of hirsutism, androgen excess, oligomenorrhea, and PCOS more effectively than late metformin. The time window of late childhood and early puberty may be more critical for the development, and thus for the prevention, of adolescent PCOS than the first years beyond menarche. Copyright © 2011 by The Endocrine Society.

Ibanez L.,University of Barcelona | Ibanez L.,Institute Salud Carlos III | Diaz M.,University of Barcelona | Diaz M.,Institute Salud Carlos III | And 6 more authors.
Journal of Clinical Endocrinology and Metabolism | Year: 2013

Background: An oral estro-progestagen is the standard medication given to adolescent girls with androgen excess, even when those girls are not at risk of pregnancy. Aim: The aim of this study was to compare on-treatment and post-treatment effects of intervention with an oral contraceptive vs an insulin-sensitizing treatment for androgen excess in nonobese adolescents. Design: This was a randomized, open-label trial. Study Population: Subjects were nonobese adolescent girls with hyperinsulinemic androgen excess and without risk of pregnancy (mean age, 16 years; body mass index, 23 kg/m2; n = 34). Interventions: The effects of treatment with ethinylestradiol- cyproteroneacetate (EE-CA) vs a lowdose combination of pioglitazone (7.5 mg/d), flutamide (62.5 mg/d), and metformin (850 mg/d) (PioFluMet) for 18 months were studied. Posttreatment follow-up was for 6 months. Main Outcome Measures: Androgen excess (hirsutism and acne scores and serum testosterone), glucose-stimulated insulinemia, circulating C-reactive protein, carotid intima media thickness, body composition (absorptiometry), abdominal fat partitioning (magnetic resonance imaging), and menstrual regularity were measured. Results: EE-CA and PioFluMet attenuated androgen excess similarly but had divergent, and even opposing, effects on other outcomes. Six months posttreatment, the PioFluMet-treated girls had a lower glucose-induced insulinemia, a lower C-reactive protein level, and a thinner intima media than the EE-CA-treated girls, and they were viscerally less adipose, had a higher lean mass, and were more likely to have regular cycles. Conclusions: The on-treatment and post-treatment effects of PioFluMet compared favorably with those of oral contraception in nonobese adolescents with androgen excess. The intervention whereby androgen excess is reduced in adolescence influences the post-treatment phenotype. PioFluMet-like interventions in adolescence may thus hold the potential to prevent part of the androgen-excess phenotype in adulthood, including adiposity and subfertility. Copyright © 2013 by The Endocrine Society.

De Zegher F.,Catholic University of Leuven | Sebastiani G.,University of Barcelona | Sebastiani G.,Institute Salud Carlos III | Diaz M.,University of Barcelona | And 7 more authors.
Diabetes | Year: 2012

Prenatal growth restraint, if followed by postnatal overweight, confers risk for adult disease including diabetes. The mechanisms whereby neonatal nutrition may modulate such risk are poorly understood. We studied the effects of nutrition (breastfeeding [BRF] vs. formula-feeding [FOF]) on weight partitioning and endocrine state (as judged by high-molecular-weight [HMW] adiponectin and IGF-I) of infants born small for gestational age (SGA). Body composition (by absorptiometry), HMW adiponectin, and IGF-I were assessed at birth and 4 months in BRF infants born appropriate for gestational age (AGA; n = 72) and SGA infants receiving BRF (n = 46) or FOF (n = 56), the latter being randomized to receive a standard (FOF1) or protein-rich formula (FOF2). Compared with AGA-BRF infants, the catchup growth of SGA infants was confined to lean mass, independently of nutrition. Compared with AGA-BRF infants, SGA-BRF infants had normal HMW adiponectin and IGF-I levels at 4 months, whereas SGA-FOF infants had elevated levels of HMW adiponectin (particularly SGA-FOF1) and IGF-I (particularly SGA-FOF2). In conclusion, neonatal nutrition seems to influence endocrinology more readily than body composition of SGA infants. Follow-up will disclose whether the endocrine abnormalities in SGA-FOF infants can serve as early markers of an unfavorable metabolic course and whether they may contribute to design early interventions that prevent subsequent disease, including diabetes. © 2012 by the American Diabetes Association.

Juez I.,Hospital Of Fuenlabrada | Rubio C.,Hospital Universitario Of Madrid Sanchinarro | Figueras J.,Dr Josep Trueta Hospital
Clinical and Translational Oncology | Year: 2011

Colorectal cancer (CRC) is the second most common cause of cancer death in Spain. Fifty percent of patients will develop colorectal liver metastases (CLM) during the course of the disease. Less than 20% of patients with CLM are initially resectable and for them 5-year disease-free survival (DFS) is about 20-25%, with a high recurrence rate. CLM is a heterogeneous disease. From a clinical point of view, four main groups can be differentiated: initially resectable, not optimally resectable, unresectable that could be resectable and unresectable that never will be likely to be resected. Treatment of CLM must be established, always, in a multidisciplinary team discussion with an analysis of prognostic factors and resectability. For patients with resectable CLM, the EORTC trial 364 demonstrated that chemotherapy plus surgery is better than surgery alone. Consequently most patients should be treated with perioperative chemotherapy based on oxaliplatin, and if resection has been done without chemotherapy, they should receive adjuvant chemotherapy after R0 resection. Based on oncological factors, the 5-year survival rate after resection of CLM ranges from 60% to only 14% with a poor score. If a patient has more than one of the poor prognostic factors he should probably be referred for preoperative (induction) chemotherapy. Only a minority of patients with CLM are amenable to surgery; therefore, efforts have been made to increase the percentage of patients who could be candidates for resection. Studies, mostly retrospective, have confirmed the ability of neoadjuvant chemotherapy (conversion chemotherapy) to render some metastases resectable. The regimens we must use depend on the KRAS mutational status and the toxicity profiles of drugs in the context of each patient. In k-ras mutated tumours we can use bevacizumab combined with standard chemotherapy or concomitant administration of the three active agents (FOLFOXIRI) in suitable patients. In k-ras wild-type patients, the combination of cetuximab and FOLFIRI-FOLFOX improved response rates and resection rate in phase III-II trials. With a lower level of evidence, panitumumab is an alternative combined with FOLFOX. Bevacizumab is also an alternative as it does not depend on KRAS status. Radiotherapy is becoming an alternative in selected patients, where surgery is not an alternative. For the majority of patients, who will never be resectable, the continuum of care with chemotherapy will be the paradigm for their management. © 2011 Feseo.

Ibanez L.,University of Barcelona | Ong K.K.,Institute of Metabolic Science | Lopez-Bermejo A.,Dr Josep Trueta Hospital | Dunger D.B.,University of Cambridge | De Zegher F.,Catholic University of Leuven
Nature Reviews Endocrinology | Year: 2014

Hyperinsulinaemic androgen excess is the most common cause of hirsutism, acne and menstrual irregularity in adolescent girls. Here, we propose that the disorder frequently originates from an absolute or relative excess of lipids in adipose tissue, and from associated changes in insulin sensitivity, gonadotropin secretion and ovarian androgen release. Girls from populations with genotypes attuned to nutritionally harsh conditions seem to be particularly vulnerable to the development of hyperinsulinaemic androgen excess in today's obesogenic environment. We propose that hirsutism, hyperandrogenaemia and menstrual irregularity (≥ 2 years after menarche) is used as a diagnostic triad for the disorder. No pharmacological therapy has been approved for girls with androgen excess; however, lifestyle intervention is essential to reduce adiposity. In girls without obesity who are not sexually active, insulin sensitization has more broadly normalizing effects than estradiol-progestogen combinations. The early recognition of girls at risk of developing hyperinsulinaemic androgen excess might enable prevention in childhood. © 2014 Macmillan Publishers Limited. All rights reserved.

Ibanez L.,University of Barcelona | Lopez-Bermejo A.,Dr Josep Trueta Hospital | Diaz M.,University of Barcelona | De Zegher F.,Catholic University of Leuven
Fertility and Sterility | Year: 2011

Objective: To study across childhood the features of small for gestational age (SGA) girls with spontaneous catch-up growth. Design: Longitudinal study (age 2-8 years). Setting: University hospital. Patient(s): Post-catch-up SGA girls (n = 18) versus healthy control girls born appropriate for gestational age (AGA; n = 13). Intervention(s): None. Main Outcome Measure(s): Height, weight, fasting glucose, insulin, IGF-I, high-molecular-weight (HMW) adiponectin, LDL and HDL cholesterol, triglycerides, body composition by absorptiometry (2-8 years); visceral fat by magnetic resonance imaging (6-8 years); bone age (by automated reading), sex hormone-binding globulin, DHEAS, and leptin (8 years). Result(s): At age 2 years, AGA and SGA girls were comparable for all study markers. Between 2 and 8 years, girls were prepubertal; AGA and SGA girls gained height, lean mass, and bone mineral content similarly; other outcomes diverged so that, at age 8, SGA girls had markedly higher levels of circulating insulin, IGF-I, DHEAS, LDL cholesterol, and leptin; lower HMW adiponectin and SHBG levels; more total and visceral fat (without being obese); and an older bone age. Conclusion(s): After completing catch-up growth and before starting puberty, SGA girls develop an ensemble that includes not only central adiposity, hyperinsulinemia, and hypoadiponectinemia but also hyperleptinemia, dyslipidemia, lower SHBG and higher DHEAS levels, and faster bone maturation. © 2011 by American Society for Reproductive Medicine.

Lopez-Bermejo A.,Dr Josep Trueta Hospital | Diaz M.,University of Barcelona | Diaz M.,Institute Salud Carlos Iii Del Ministerio Of Ciencia E Innovacion | Moran E.,University of Barcelona | And 3 more authors.
Diabetes Care | Year: 2010

OBJECTIVE - Serine-threonine kinase STK11 catalyzes the AMP-activated protein kinase complex. We tested the hypothesis that a gene variant in STK11 contributes to variation in insulin sensitivity and metformin efficacy. RESEARCH DESIGN AND METHODS - We studied the effects of a single nucleotide polymorphism (SNP) (rs8111699) in STK11 on endocrine-metabolic and body composition indexes before and after 1 year of metformin in 85 hyperinsulinemic girls with androgen excess, representing a continuum from prepuberal girls with a combined history of low birth weight and precocious pubarche over to postmenarchial girls with hyperinsulinemic ovarian hyperandrogenism. Metformin was dosed at 425 mg/day in younger girls and 850 mg/day in older girls. STK11 rs8111699 was genotyped. Endocrine-metabolic features were assessed in the fasting state; body composition was estimated by absorptiometry. RESULTS - Genotype effects were similar in younger and older girls. At baseline, the mutated G allele in STK11 rs8111699 was associated with higher insulin and IGF-I levels (both P < 0.005). The response to metformin differed by STK11 genotype: GG homozygotes (n = 24) had robust metabolic improvements, GC heterozygotes (n = 38) had intermediate responses, and CC homozygotes (n = 23) had almost no response. Such differences were found for 1-year changes in body composition, circulating insulin, IGF-I, free androgen index, and lipids (all P < 0.005). CONCLUSIONS - In hyperinsulinemic girls with androgen excess, the STK11 rs8111699 SNP influences insulin sensitivity and metformin efficacy, so that the girls with the least favorable endocrine-metabolic profile improve most with metformin therapy. © 2010 by the American Diabetes Association.

Nuzzo G.,Catholic University of the Sacred Heart | Giordano M.,Catholic University of the Sacred Heart | Giuliante F.,Catholic University of the Sacred Heart | Lopez-Ben S.,Dr Josep Trueta Hospital | And 2 more authors.
European Journal of Surgical Oncology | Year: 2011

Background: Resection of liver tumours with involvement of inferior vena cava (IVC) is considered to have a high surgical risk. Aim: We retrospectively reviewed 23 patients who underwent hepatectomy with IVC resection in two West-European liver surgery Units. Methods: The tumours included liver metastases (n = 13), hepatocellular carcinoma (n = 4), intrahepatic cholangiocarcinoma (n = 3), liver haemangioma (n = 1), primary hepatic lymphoma (n = 1) and recurrent right adrenal gland carcinoma (n = 1). Results: IVC resection was associated with right hepatectomy in 8 cases, extended right hepatectomy in 9 cases, extended left hepatectomy in 3 cases, minor liver resection in 2 cases, and right hepatectomy with nephrectomy in one case. In 16 patients the IVC wall involvement was <30% of its circumference, and a tangential vena cava resection was performed. In 7 patients (30%) with >50% involvement, a caval segment was resected and replaced with a 20 mm ringed polytetrafluoroethylene graft. R0-resection was achieved in all patients. Median intraoperative blood loss was 1.100 ml (range 490-15,000). Fourteen patients were transfused with a median of 3 PRC units per patient (range 1-25). Major complications occurred in 9 patients. Postoperative stay in ICU was 2.3 ± 3.4 days (range 1-14) and hospital stay was 17.3 ± 2.6 days (range 5-62). In 14 patients, final pathology demonstrated microscopic IVC infiltration. Conclusions: In selected patients with malignant involvement of the liver and IVC, surgical resection en bloc with IVC is the only possibility to achieve R0 resection, with acceptable mortality and morbidity, in units specialized in liver surgery. © 2011 Elsevier Ltd. All rights reserved.

Scalzone R.,Dr Josep Trueta Hospital | Lopez-Ben S.,Dr Josep Trueta Hospital | Figueras J.,Dr Josep Trueta Hospital
Digestive Surgery | Year: 2012

There is a close relationship between blood loss during transection and unfavorable outcome. Many different methods have been used in order to cut the parenchyma, while leaving vital structures intact, coagulate small vessels and seal small biliary ducts. The first method described was the finger-fracture technique and, alternatively, the clamp-crushing method using a small forceps. With this technique, the liver is crushed between the 'jaws', and the vessels and bile ducts are successively ligated and divided. Technological research using different sources of energy developed the water jet dissectors and the ultrasonic dissectors. The CUSA® has been widely adopted for the fascinating way it could selectively destroy and aspirate parenchyma leaving vascular structures almost intact. Several studies have been addressed to clarify these critical points. However, in the majority of cases they are underpowered to demonstrate clear advantages of one method over the others. In conclusion, the evidence suggested no superiority of other techniques over clamp-crushing. But it must be taken into account that it requires strictly hepatic pedicle clamping. The devices available should be used within the limits of each instrument, as well as the surgical skills of the surgeon. Probably the best option should be a combined approach. © 2012 S. Karger AG, Basel.

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