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The authors regret that the author list in reference 27 was written incorrectly and should have been as follows: 27. M. Donker, M.E Straver, J. Wesseling, C.E. Loo, M. Schot, C.A Drukker et al. Marking axillary lymph nodes with radioactive iodine seeds for axillary staging after neoadjuvant systemic treatment in breast cancer patients: the MARI procedure. Ann Surg, 261 (2) (2015), pp. 378-382 The authors would like to apologise for any inconvenience caused.

Bariatric surgery procedures are more and more performed in women of reproductive age, whose fertility often increases after weight loss, so they frequently become pregnant. In this condition they require appropriate management, according to the type of procedure, malabsorptive or restrictive. If health risks related to obesity (gestational diabetes, pregnancy induced hypertension, pre-eclampsia) decrease after weight loss, other risks related to bariatric procedures could appear. LAGB is a safe and well-tolerated procedure, but some complications could appear more frequently during pregnancy; some symptoms could be suggestive for important complications, that if not treated in the best way could threaten mother and child's health. Emesis of the first trimester could favor slippage, thus influencing feeding and fetal growth. The slippage of the band is a common complication of LAGB, that usually does not lead to serious conditions, but in our case the pregnant risked a lot because of malnutrition. The purpose of this article is to present an obstetric case study of a woman who experienced this complication postbariatric surgery and the implications for mother and child. A correct diagnosis and management of the clinical case led to a positive conclusion, thus underlining bariatric surgery and its complications should be known and taken into account by every physician.

Surgical site infections (SSIs) are recognized as a common surgical complication, occurring in about 2-5% of all surgical procedures. SSIs represent the third most frequent nosocomial infection, accounting for 14.6% of all infections observed in hospitalised patients and 38% of those observed among surgical patients. Strategies for the prevention of SSIs also include surveillance which has proved very effective. The most recent surveillance study carried out at a national level in Italy is Kir-Nos, a multicentric study sponsored by GlaxoSmithKline and performed between April and June 2002 in 32 different General Surgery Units for a total of 2972 surgical patients enrolled. Results emerging from the study clearly indicate that many patients receive inappropriate antimicrobial prophylaxis, especially in terms of drug choice, route and timing of administration. Given the high economic burden that infections provoke, beyond the increased morbidity and mortality, it appears mandatory to improve our tools in order to reduce their incidence, as a reduction of only 0.1% can result in a considerable saving of economic resources to be allocated to other activities, such as screening and prevention programs.

Oncogene-induced reactive oxygen species (ROS) have been proposed to be signaling molecules that mediate proliferative cues. However, ROS may also cause DNA damage and proliferative arrest. How these apparently opposite roles can be reconciled, especially in the context of oncogene-induced cellular senescence, which is associated both with aberrant mitogenic signaling and DNA damage response (DDR)-mediated arrest, is unclear. Here, we show that ROS are indeed mitogenic signaling molecules that fuel oncogene-driven aberrant cell proliferation. However, by their very same ability to mediate cell hyperproliferation, ROS eventually cause DDR activation. We also show that oncogenic Ras-induced ROS are produced in a Rac1 and NADPH oxidase (Nox4)-dependent manner. In addition, we show that Ras-induced ROS can be detected and modulated in a living transparent animal: the zebrafish. Finally, in cancer we show that Nox4 is increased in both human tumors and a mouse model of pancreatic cancer and specific Nox4 small-molecule inhibitors act synergistically with existing chemotherapic agents. © 2014 Macmillan Publishers Limited All rights reserved.

Relations between laparoscopic adjustable gastric banding (LAGB), gastroesophageal reflux (GER) and hiatal hernia (HH) are controversial. In this context the role of preoperative investigations to assess upper gastrointestinal (GI) function and its impact on the approach to LAGB and outcomes remains unclear. The aim was to define the value of preoperative upper GI testing, and to relate the findings with postoperative outcomes.Seventy-eight cases were enrolled among 250 patients undergoing LAGB from January 2010 to December 2011 in our Center for the Multidisciplinary treatment of severe obesity. Patients were submitted preoperatively to endoscopy and radiologic series with oral contrast to assess the state of upper GI mucosa, the presence of HH, GER or cardias incontinence. According to the findings, patients were assigned to group A, if one or both exams showed positive results; or to the control group B if both exams were negative.GI series showed GER in 14.1% of patients, HH in 6.4%, altered motility in 5.1%, gastritis in 3.1%and were negative in 75.6%. Endoscopy showed gastritis in 71.8%of patients, HH in 30.8%, esophagitis in 7.7%, duodenitis in 7.7%, LES incontinence in 8%; while only 21.8% of patients had a negative exam. Differences between group A and B are not statistically significant in terms of pre- and post-operative BMI, EBWL%, long-term complications, time and number of regulations.Positive findings in preoperative testing rarely postpone or change the surgical approach and postoperative outcomes. Our results encourage the omission of upper GI series from routine evaluation protocol prior to LAGB.

Laparoscopic sleeve gastrectomy (LSG) is a stand-alone bariatric procedure, its feasibility and efficacy being confirmed by long-term data. The effect of the procedure is believed to be based on the gastric restriction and reduction of ghrelin. Nevertheless it remains still controversial the role of LSG on gastric emptying and the impact that this may have on weight loss outcomes. Our aim is to assess gastric emptying after LSG using gastric scintigraphy.For this prospective randomized study, 45 patients undergoing LSG at our Centre for the Multidisciplinary Treatment of Severe Obesity from April 2009 to April 2011 were enrolled and observed prospectively (Group A). The inclusion criteria followed the guidelines for bariatric surgery. All patients performed gastric emptying scintigraphy through a standard semisolid meal (250 kcal), marked with 0.5 mCiTc 99. Group A performed the exam before (A1) and after the operation (A2). A control group (Group B) included 20 patients undergoing scintigraphic assessment for other reasons.LSG was performed following a standardized technique. No complications were observed. The scintigraphic study showed a reduced half-life tracer (A1 vs. A2: 80.4±16.5 min vs. 64.3±22 min P=0.06), without a significant difference. Comparing the two groups no differences occurred before operation (B vs. A1). Gastric emptying time resulted significatively reduced in group A2 rather than in group A1 and B.Gastric motility plays a role in the pathogenesis of obesity. Our experience suggests that LSG reduces gastric emptying time, but further studies are necessary to reach statystical significativity.

Activating mutations in the BRAF-MAPK pathway have been reported in histiocytoses, hematological inflammatory neoplasms characterized by multi-organ dissemination of pro-inflammatory myeloid cells. Here, we generate a humanized mouse model of transplantation of human hematopoietic stem and progenitor cells (HSPCs) expressing the activated form of BRAF (BRAFV600E). All mice transplanted with BRAFV600E-expressing HSPCs succumb to bone marrow failure, displaying myeloid-restricted hematopoiesis and multi-organ dissemination of aberrant mononuclear phagocytes. At the basis of this aggressive phenotype, we uncover the engagement of a senescence program, characterized by DNA damage response activation and a senescence-associated secretory phenotype, which affects also non-mutated bystander cells. Mechanistically, we identify TNFα as a key determinant of paracrine senescence and myeloid-restricted hematopoiesis and show that its inhibition dampens inflammation, delays disease onset and rescues hematopoietic defects in bystander cells. Our work establishes that senescence in the human hematopoietic system links oncogene-activation to the systemic inflammation observed in histiocytic neoplasms., BRAF-MAPK activating mutations are reported in histiocytoses—hematological neoplasms with widespread pro-inflammatory myeloid cells. Here, the authors show that an activating mutant BRAF in haematopoietic stem and progenitor cells causes an oncogene-induced senescence response leading to myeloid restricted haematopoiesis, inflammation and histiocytosis.

Over the past decades, our molecular understanding of acute myeloid leukemia (AML) pathogenesis dramatically increased, thanks also to the advent of next-generation sequencing (NGS) technologies. Many of these findings, however, have not yet translated into new prognostic markers or rationales for treatments. We now know that AML is a highly heterogeneous disease characterized by a very low mutational burden. Interestingly, the few mutations identified mainly reside in epigenetic regulators, which shape and define leukemic cell identity. In the light of these discoveries and given the increasing number of drugs targeting epigenetic regulators in clinical development and testing, great interest is emerging for the use of small molecules targeting leukemia epigenome. Together with their effects on leukemia cell-intrinsic properties, such as proliferation and survival, epigenetic drugs may affect the way leukemic cells communicate with the surrounding components of the tumor and immune microenvironment. Here, we review current knowledge on alterations in the AML epigenetic landscape and discuss the promises of epigenetic therapies for AML treatment. Finally, we summarize emerging molecular studies elucidating how epigenetic rewiring in cancer cells may as well exert immune-modulatory functions, boost the immune system, and potentially contribute to better patient outcomes.

Introduction Laparoscopic Adjustable Gastric Banding (LAGB) is a safe and effective treatment for obesity. A strong evidence links weight loss with improved fertility outcomes and reduced gestational complications in subsequent pregnancies. Our aim is to describe the impact of LAGB on maternal and neonatal outcomes. Methods Data were collected retrospectively from the database of our University Center for the Multicentric Treatment of Severe Obesity. From January 2006 to December 2011, 438 patients underwent LAGB. Of these, 140 women of reproductive age (18–46 years old) were included in our study. The following parameters were registered during follow-up: number of pregnancies, delivery and miscarriage, time from LAGB to pregnancy, band adjustments, weight gain during pregnancy, gestational and obstetrical complications (gestational diabetes mellitus, hypertensive disorders, prolonged labor), mode of delivery, neonatal birth weight and complications (low birth weight, IUGR, prematurity, macrosomy). Results We registered 26 pregnancies with a total of 22 babies born and 4 miscarriages. The mean time from LAGB to pregnancy was 15.8 months. Band adjustments were performed in 100% of patients during the first trimester; the average weight gain at the end of pregnancy was 14.66 kg. None presented gestational or obstetrical complications. One patient presented band slippage, which required surgery, and one patient presented iron-deficiency anemia. 100% of deliveries were by cesarean section. No perinatal complications or malformations were recorded, and the average baby weight was 3027 g. Conclusion LAGB is a safe procedure, well tolerated during pregnancy and without negative implications on both the mother and the baby. According to our experience and recent studies, band loosening should be reserved to symptomatic patients to avoid unhealthy weight gain.

Introduction The potential advantages of oncoplastic breast conserving surgery (BCS) have not been validated in robust studies that constitute high levels of evidence, despite oncoplastic techniques being widely adopted around the globe. There is hence the need to define the precise role of oncoplastic BCS in the treatment of early breast cancer, with consensual recommendations for clinical practice. Methods A panel of world-renowned breast specialists was convened to evaluate evidence, express personal viewpoints and establish recommendations for the use of oncoplastic BCS as primary treatment of unifocal early stage breast cancers using the GRADE approach. Results According to the results of the systematic review of literature, the panelists were asked to comment on the recommendation for use of oncoplastic BCS for treatment of operable breast cancer that is suitable for breast conserving surgery, with the GRADE approach. Based on the voting outcome, the following recommendation emerged as a consensus statement: Oncoplastic breast conserving surgery should be recommended versus standard breast conserving surgery for the treatment of operable breast cancer in adult women who are suitable candidates for breast conserving surgery (with very low certainty of evidence). Discussion This review has revealed a low level of evidence for most of the important outcomes in oncoplastic surgery with lack of any randomized data and absence of standard tools for evaluation of clinical outcomes and especially patients’ values. Despite areas of controversy, about one-third (36%) of panel members expressed a strong recommendation in support of oncoplastic BCS. Presumably, this reflects a synthesis of views on the relative complexity of these techniques, associated complications, impact on quality of life and costs.