Microstructure, surface characterization and long-term stability of new quaternary Ti-Zr-Ta-Ag alloy for implant use.

The novel Ti-20Zr-5Ta-2Ag alloy was characterised concerning its microstructure, morphology, mechanical properties, its passive film composition and thickness, its long-term electrochemical stability, corrosion resistance, ion release rate in Ringer solution of acid, neutral and alkaline pH values and antibacterial activity. The new alloy has a crystalline α microstructure (by XRD). Long-term XPS and SEM analyses show the thickening of the passive film and the deposition of hydroxyapatite in neutral and alkaline Ringer solution. The values of the electrochemical parameters confirm the over time stability of the new alloy passive film. All corrosion parameters have very favourable values in time which attest a high resistance to corrosion. Impedance spectra evinced a bi-layered passive film formed by the barrier, insulating layer and the porous layer. The monitoring of the open circuit potentials indicated the stability of the protective layers and their thickening in time. The new alloy releases (by ICP-MS measurements) very low quantities of Ti, Zr, Ag ions and no Ta ions. The new alloy exhibits a low antibacterial activity.

Open vs robotic radical gastrectomy for locally advanced gastric cancer.

BACKGROUND: This study aims to evaluate the immediate outcomes of robotic and open gastrectomy for patients with locally advanced gastric adenocarcinomas. METHODS: A retrospective analysis was performed on patients undergoing curative intent gastrectomies between 2004 and 2013 in our department. Operative and postoperative outcomes as well as long-term survival data were analysed. RESULTS: Two groups of patients were analysed: the robotic group (n = 18) and the open surgery group (n = 29). Operating time in the robotic group (320.833 ± 85.186 min) was significantly longer (p = 0.0004) as compared with the open group (243.366 ± 57.973 min). The number of retrieved lymph nodes was not statistically different between the two groups (p = 0.108) and neither was the rate of postoperative complications (p = 0.294). CONCLUSIONS: Robotic gastrectomy is a safe procedure, with satisfactory short- and long-term outcomes in locally advanced gastric cancer. Studies on a larger number of patients are necessary in order to confirm whether an immediate benefit in survival exists due to robotic surgery. Copyright © 2015 John Wiley & Sons, Ltd.

Robotically performed total mesorectal excision for rectal cancer.

BACKGROUND: Rectal cancer is an important health problem, due to the increasing number of new cases and the quality of life issues brought forth by surgical treatment in these patients. AIM: The aim of the study was to analyse the results of robotic surgery in the treatment of lower and middle rectal cancer,locations in which TME is performed. MATERIAL AND METHOD: Patients diagnosed with and operated on for rectal cancer by the means of robotic surgery between 2008-2012 at the Fundeni Clinical Institute were retrospectively analysed. RESULTS: A number of 117 patients with rectal cancer were operated on by robotic surgery, of which 79 (67.52%) were submitted to total mesorectal excision (TME). The most frequently performed surgery was low anterior resection, followed by rectal amputation through abdominoperineal approach.Anastomosis fistula was observed in 9 (11.39%) patients. Local recurrence was encountered in 2 (2.53%) of the robotically performed surgeries. CONCLUSIONS: 1. Robotically assisted total mesorectal excision is feasible, safe and can be performed with a small number of complications and a low local recurrence rate; 2. The main advantages are oncological safety and quality of life; 3.Conversion to open surgery is rarely encountered; 4. Protection loop ileostomy existence allows avoiding reintervention in case anastomotic fistula occurs in patients with low anterior resection. 5. Robotic surgery may become gold standard in the surgical treatment of rectal cancer.

Cellular and Kaposi's sarcoma-associated herpes virus microRNAs in sepsis and surgical trauma.

Once a patient is in septic shock, survival rates drop by 7.6% for every hour of delay in antibiotic therapy. Biomarkers based on the molecular mechanism of sepsis are important for timely diagnosis and triage. Here, we study the potential roles of a panel of cellular and viral miRNAs as sepsis biomarkers. We performed genome-wide microRNA (miRNA) expression profiling in leukocytes from septic patients and nonseptic controls, combined with quantitative RT-PCR in plasmas from two cohorts of septic patients, two cohorts of nonseptic surgical patients and healthy volunteers. Enzyme-linked immunosorbent assay, miRNA transfection and chromatin immunoprecipitation were used to study the effects of Kaposi sarcoma herpes virus (KSHV) miRNAs on interleukin's secretion. Differences related to sepsis etiology were noted for plasma levels of 10 cellular and 2 KSHV miRNAs (miR-K-10b and miR-K-12-12*) between septic and nonseptic patients. All the sepsis groups had high KSHV miRNAs levels compared with controls; Afro-American patients had higher levels of KSHV-miR-K12-12* than non-Afro-American patients. Both KSHV miRNAs were increased on postoperative day 1, but returned to baseline on day 7; they acted as direct agonists of Toll-like receptor 8 (TLR8), which might explain the increased secretion of the IL-6 and IL-10. Cellular and KSHV miRNAs are differentially expressed in sepsis and early postsurgical patients and may be exploited for diagnostic and therapeutic purposes. Increased miR-K-10b and miR-K12-12* are functionally involved in sepsis as agonists of TLR8, forming a positive feedback that may lead to cytokine dysregulation.

Potentiality of the "Gum Metal" titanium-based alloy for biomedical applications.

In this study, the "Gum Metal" titanium-based alloy (Ti-23Nb-0.7Ta-2Zr-1.2O) was synthesized by melting and then characterized in order to evaluate its potential for biomedical applications. Thus, the mechanical properties, the corrosion resistance in simulated body fluid and the in vitro cell response were investigated. It was shown that this alloy presents a very high strength, a low Young's modulus and a high recoverable strain by comparison with the titanium alloys currently used in medicine. On the other hand, all electrochemical and corrosion parameters exhibited more favorable values showing a nobler behavior and negligible toxicity in comparison with the commercially pure Ti taken as reference. Furthermore, the biocompatibility tests showed that this alloy induced an excellent response of MC3T3-E1 pre-osteoblasts in terms of attachment, spreading, viability, proliferation and differentiation. Consequently, the "Gum Metal" titanium-based alloy processes useful characteristics for the manufacturing of highly biocompatible medical devices.

Benign cystic neoplasm and endocrine tumours of the pancreas--when and how to operate--an overview.

BACKGROUND: The recent evolution of limited local operative procedures for benign pancreatic lesions shifted surgical treatment options to the application of local techniques, although major resections of pancreatic head and left resection are still the standard. OBJECTIVES: To evaluate the level of evidence of tumour enucleation (EN), pancreatic middle segment resection (PMSR) and duodenum preserving total/subtotal pancreatic head resection (DPPHRt/s), we focus based on present knowledge on indication to surgical treatment evaluating the questions, when and how to operate. RESULTS: Tumour enucleation is recommended for all symptomatic neuro-endocrine tumours with size up to 2-3 cm and non-adherence to pancreatic main-ducts. EN has been applied predominantly in neuro-endocrine tumours and less frequently in cystic neoplasms. 20% of enucleation are performed as minimal invasive laparascopic procedure. Surgery related severe post-operative complications with the need of re-intervention are observed in about 11%, pancreatic fistula in 33%. The major advantage of EN are low procedure related early post-operative morbidity and a very low hospital mortality. PMSR is applied in two thirds for symptomatic cystic neoplasm and in one third for neuro-endocrine tumours. The high level of 33% pancreatic fistula and severe post-operative complications of 18% is related to management of proximal pancreatic stump. DPPHRt/s is used in 70% for symptomatic cystic neoplasms, for lesions with risk for malignancy and in less than 10% for neuro-endocrine tumours. DPPHRt with segment resection of peripapillary duodenum and intra-pancreatic common bile duct has been applied in one third of patients and in two thirds by complete preservation of duodenum and common bile duct. The level of evidence for EN and PMSR is low because of retrospective data evaluation and absence of RCT results. For DPPHR, 7 prospective, controlled studies underline the advantages compared to partial pancreaticoduodenectomy. CONCLUSION: The application of tumour enucleation, pancreatic middle segment resection and duodenum preserving subtotal or total pancreatic head resection are associated with low level surgery related early post-operative complications and a very low hospital mortality. The major advantage of the limited procedures is preservation of exo- and endocrine pancreatic functions.

Design of a nitrogen-implanted titanium-based superelastic alloy with optimized properties for biomedical applications.

In this study, a superelastic Ni-free Ti-based biomedical alloy was treated in surface by the implantation of nitrogen ions for the first time. The N-implanted surface was characterized by X-ray diffraction, X-ray photoelectron spectroscopy, and secondary ion mass spectroscopy, and the superficial mechanical properties were evaluated by nano-indentation and by ball-on-disk tribological tests. To investigate the biocompatibility, the corrosion resistance of the N-implanted Ti alloy was evaluated in simulated body fluids (SBF) complemented by in-vitro cytocompatibility tests on human fetal osteoblasts. After implantation, surface analysis methods revealed the formation of a titanium-based nitride on the substrate surface. Consequently, an increase in superficial hardness and a significant reduction of friction coefficient were observed compared to the non-implanted sample. Also, a better corrosion resistance and a significant decrease in ion release rates have been obtained. Cell culture experiments indicated that the cytocompatibility of the N-implanted Ti alloy was superior to that of the corresponding non-treated sample. Thus, this new functional N-implanted titanium-based superelastic alloy presents the optimized properties that are required for various medical devices: superelasticity, high superficial mechanical properties, high corrosion resistance and excellent cytocompatibility.

[A paediatrician's play kit: example and basic tool for an approach of the infant's global development between 0 and 4 years of age]. / Une mallette de jeux du pédiatre: exemple d'un outil de base pour l'approche du développement global chez l'enfant entre zéro et quatre ans.

The South and West Francilien Pediatric Network (Réseau Pédiatrique du Sud et Ouest Francilien [RPSOF]) has established a protocol for the developmental follow up of infants inspired by the existing developmental scales adapted to the current practice of out patient consultation. The consultation described here collects a set of very simple objects and trade toys that are a support for a qualitative exploration of the development for the infants of less than 4 years of age. Different fields are taken into account: global motor skills, hand-eye coordination, manipulation and construction, communication and language, attentional capacity, relational and social behaviour. The time of exchange and play between the paediatrician and the infant allows a first detection of possible problems: the orientation towards a specialized professional for a consultation, a standard check-up or even a therapeutic care becomes easier and clearer. This playful environment also offers a space for the parents, and supports their participation as primary role players in the development of their child. This time, integral part of the consultation, is completed by the somatic examination and sensory screening tests. At present reserved for children identified as being at risk, this type of consultation could be universalised for all infants.

Robotic surgery for rectal cancer: a single center experience of 100 consecutive cases.

BACKGROUND: Minimally invasive techniques have revolutionized the field of general surgery over the few last decades. Despite its advantages, in complex procedures such as rectal surgery, laparoscopy has not achieved a high penetration rate because of its steep learning curve, its relatively high conversion rate and technical challenges. The aim of this study was to present a single center experience with robotic surgery for rectal cancer focusing mainly on early and mid-term postoperative outcome. METHODS: A series of 100 consecutive patients who underwent robotic rectal surgery between January 2008 and June 2012 was analyzed retrospectively in terms of demographics, pathological data, surgical and oncological outcomes. RESULTS: Seventy-seven patients underwent robotic sphincter-saving resection, and 23 patients underwent robotic abdominoperineal resection. There were 4 conversions. The median operative time for sphincter-saving procedures was 180 min. The median time for robotic abdominoperineal resection was 160 min. The median distal resection margin of the operative specimen was 3 cm. The median number of retrieved lymph nodes was 14. The median hospital stay was 10 days. In-hospital mortality was nil. The overall morbidity was 30%. Four patients presented transitory postoperative urinary dysfunction. Severe erectile dysfunction was reported by 3 patients. The median length of follow-up was 24 months. The 3-year overall survival rate was 90%. CONCLUSIONS: Robotic surgery is advantageous for both surgeons (in that it facilitates dissection in a narrow pelvis) and patients (in that it affords a very good quality of life via the preservation of sexual and urinary function in the vast majority of patients and it has low morbidity and good midterm oncological outcomes). In rectal cancer surgery, the robotic approach is a promising alternative and is expected to overcome the low penetration rate of laparoscopy in this field.

[Experience of parents after the loss of a newborn twin in the NICU: a qualitative study 3 years after the death]. / Vécu de parents ayant perdu un jumeau en réanimation néonatale : étude qualitative, 3 ans après le décès.

INTRODUCTION: The mortality rate both before and after birth is higher in twins. Parents face a particularly difficult mourning experience when confronted with the loss of 1 of their newborn twins. The aim of this article is to describe how parents experience and cope with this situation over the long term, how they describe the loss at the time of the death in a neonatal intensive care unit (NICU), the way they are able to become attached to the surviving twin, and the role that NICU caregivers can play to help them. METHOD AND POPULATION: This study is part of a larger qualitative study on parental mourning after the loss of a newborn in 4 NICUs in France. Semi-structured research interviews were conducted 3years after the death. The interviews were recorded, transcribed, and anonymized. Discourse analysis was used to extract the data on different themes. Among the 166 participating parents, 26 had lost a newborn twin. RESULTS: The parents reported their difficulties when faced with simultaneous contradictory events at the time of the death of a twin child in the NICU. Mourning appeared to be more difficult in this particular case: to combine the loss of a deceased child with the care of the surviving newborn was very complicated. The existence of the "co-twin" was described as an essential support for the parents; however, over the long term, this child could not fulfill the feelings of emptiness. The relation with this surviving child was sometimes disturbed by parental anxiety that the accident could recur. Fathers and mothers showed repression of their sadness and despair. The representations of the 2 children in their parents' mind were sometimes very close or even overlapping and some parents were confused with regards to the place each of them could have. In the NICU, the caregivers should be able to listen to the parents expressing their contradictory feelings, to sustain the acknowledgement of the loss of 1 child, and in becoming attached to the surviving child. Parents need to be reassured about their living child's health. CONCLUSION: When faced with the loss of a newborn twin, parents are overwhelmed by the coexistence of contradictory feelings. The role of the medical staff is essential in building separate stories and having different memories for each child.

Robotic surgery of locally advanced gastric cancer: a single-surgeon experience of 41 cases.

The mainstay of curative gastric cancer treatment is open gastric resection with regional lymph node dissection. Minimally invasive surgery is yet to become an established technique with a well defined role. Robotic surgery has by-passed some of the limitations of conventional laparoscopy and has proven both safe and feasible. We present our initial experience with robotic surgery based on 41 gastric cancer patients. We especially wish to underline the advantages of the robotic system when performing the digestive tract anastomoses. We present the techniques of end-to-side eso-jejunoanastomoses (using a circular stapler or manual suture) and side-to-side eso-jejunoanastomoses. In our hands, the results with circular stapled anastomoses were good and we advocate against manual suturing when performing anastomoses in robotic surgery. Moreover, we recommend performing totally intracorporeal anastomoses which have a better post-operative outcome, especially in obese patients. We present three methods of realising the total intracorporeal eso-jejuno-anastomosis with a circular stapler: manual purse-string suture, using the OrVil and the double stapling technique. The eso-jejunoanastomosis is one of the most difficult steps in performing the total gastrectomy, but these techniques allow the surgeon to choose the best option for each case. We consider that surgeons who undertake total gastrectomies must have a special training in performing these anastomoses.

A clinical case of Fournier gangrene.

OBJECTIVE: To present a case of Fournier gangrene and the specific surgical therapy CASE PRESENTATION: A 71-year old patient with a two days history of pain in the perineal region, swelling, developing necrosis and foul-smelling lesions was examined in emergency settings. The swelling of subcutaneous plane involved the flank regions, mainly on the left side. The investigations were performed (full blood count, blood urea, electrolytes, coagulation profile). A Fournier gangrene was diagnosed and surgery performed under general anesthesia. Broad spectrum antibiotics were given concomitantly. The first surgical procedure consisted in surgical debridement and excision of all the necrotic tissue. Cultures were taken. We performed counter incisions bilaterally on both flanks. The communication through the fascial planes was clearly demonstrated, especially on the left side. A loop colostomy was also performed. Multiple re-excisions were further employed. Due to a precarious evolution, the patient were on mechanical ventilation for 13 days. Inotrope medication was given for a total of 19 days and, the antibiotherapy adapted to the antibiogram (Bacterioides eggerthii was identified). The reconstruction of the perineum was later performed and, after 3 months, the colostomy was closed in good conditions without further complications. CONCLUSION: Early recognition and aggressive surgical excision are mandatory for success in patients with Fournier gangrene. Colonic diversion can be very useful if employed from the beginning.

Surface characterization and biocompatibility of titanium alloys implanted with nitrogen by Hardion+ technology.

In this study, the new Hardion+ micro-implanter technology was used to modify surface properties of biomedical pure titanium (CP-Ti) and Ti-6Al-4V ELI alloy by implantation of nitrogen ions. This process is based on the use of an electron cyclotron resonance ion source to produce a multienergetic ion beam from multicharged ions. After implantation, surface analysis methods revealed the formation of titanium nitride (TiN) on the substrate surfaces. An increase in superficial hardness and a significant reduction of friction coefficient were observed for both materials when compared to non-implanted samples. Better corrosion resistance and a significant decrease in ion release rates were observed for N-implanted biomaterials due to the formation of the protective TiN layer on their surfaces. In vitro tests performed on human fetal osteoblasts indicated that the cytocompatibility of N-implanted CP-Ti and Ti-6Al-4V alloy was enhanced in comparison to that of the corresponding non treated samples. Consequently, Hardion+ implantation technique can provide titanium alloys with better qualities in terms of corrosion resistance, cell proliferation, adhesion and viability.

Robotic surgery of locally advanced gastric cancer -- an initial experience.

BACKGROUND: The treatment of gastric cancer is currently based on open gastric resection and regional lymph node dissection. Although the minimally invasive approach is currently being adopted for ever more complex procedures in order to improve post-operative outcomes, the laparoscopic radical D2 gastrectomy has not yet gained a wide acceptance, it being considered one of the most difficult operations in general surgery. Robotic surgery is better than the conventional laparoscopic approach, in that it avoids some of its limitations. Wristed instruments with seven degrees of freedom, the tremor filtering system, the ability to scale motion, and tridimensional vision improve the surgeons' dexterity when a fine manipulation of tissues in a narrow, fixed operating field or handsewn sutures are required. This study will attempt to evaluate the feasibility of robotic total and subtotal gastrectomy for locally advanced gastric cancer. METHODS: Two patients with locally advanced gastric adenocarcinoma underwent robot-assisted gastrectomy with D2 lymph node dissection, with no open or laparoscopic conversion. RESULTS: The post-operative evolution was uneventful and they were both discharged without complications. The number of lymph nodes retrieved was comparable to open surgery. Currently, after a follow-up period of 23 and 26 months respectively, both patients are disease-free. CONCLUSIONS: Robotic surgery can be a simpler way of expanding the indications of minimally invasive surgery so as to include the advanced gastric cancer. However, controlled prospective studies are needed in order to evaluate the role of robotics in the management of gastric cancer.

Fractal-like kinetics, a possible link between preconditioning and sepsis immunodepression. On the chemical basis of innate immunity.

In a recent paper the authors hypothesized that the so called fractal-like enzyme kinetics of intracellular reactions may explain the preconditioning effect in biology (Vasilescu C, Olteanu M, Flondor P, Revue Roumaine de Chimie. 2011; 56(7): 751-7). Inside cells the reaction kinetics is very well described by fractal-like kinetics. In the present work some clinical implications of this model are analyzed. Endotoxin tolerance is a particular case of preconditioning and shows similarities with the immunodepression seen in some sepsis patients. This idea offers a theoretical support for modulation of the enzymatic activity of the cell by changing the fractal dimension of the cytoskeleton.

[Current problems in surgical oncology. Part 3. Total mesorectal excision with curative intent. Why are not all patients with rectal cancer treated with minimally invasive procedures (either by laparoscopy or by robotic surgery)?]. / Probleme de chirurgie oncologica. 3. Despre excizia totala a mezorectului, cu sinceritate. De ce nu sunt toate cancerele rectale operate minimal invaziv (nici laparoscopic, nici robotic)?

The main evaluation criterion in rectum cancer surgery is the accuracy of total mesorectal excision (TME). Laparoscopic TME has some advantages (sharp dissection, a better visibility) over open surgery; there are other factors that limited the dissemination of the laparoscopic approach (rigid instruments, with a limited maneuverability). Laparoscopic TME can be beneficial for selected patients. Robotic surgery, with a better view and instrument versatility, may overcome in part the limitations of laparoscopic TME. The excellent results demonstrated by robotic surgery in other types of pelvic malignancies (in urology and gynecology) are expected in the treatment of rectum cancer surgery. However, still remain patients with advanced rectum cancers that can be operated correctly only by open surgery. Laparoscopy and robotics are only tools and not aims of the oncological surgery.

Mechanical and corrosion resistance of a new nanostructured Ti-Zr-Ta-Nb alloy.

In this work, a multi-elementary Ti-10Zr-5Nb-5Ta alloy, with non-toxic alloying elements, was used to develop an accumulative roll bonding, ARB-type procedure in order to improve its structural and mechanical properties. The alloy was obtained by cold crucible semi-levitation melting technique and then was ARB deformed following a special route. After three ARB cycles, the total deformation degree per layer is about 86%; the calculated medium layer thickness is about 13 µm. The ARB processed alloy has a low Young's modulus of 46 GPa, a value very close to the value of the natural cortical bone (about 20 GPa). Data concerning ultimate tensile strength obtained for ARB processed alloy is rather high, suitable to be used as a material for bone substitute. Hardness of the ARB processed alloy is higher than that of the as-cast alloy, ensuring a better behaviour as a implant material. The tensile curve for the as-cast alloy shows an elastoplastic behaviour with a quite linear elastic behaviour and the tensile curve for the ARB processed alloy is quite similar with a strain-hardening elastoplastic body. Corrosion behaviour of the studied alloy revealed the improvement of the main electrochemical parameters, as a result of the positive influence of ARB processing. Lower corrosion and ion release rates for the ARB processed alloy than for the as-cast alloy, due to the favourable effect of ARB thermo-mechanical processing were obtained.

[Current problems in surgical oncology 2. A lesson from Japan. D2 lymphadenectomy in gastric cancer]. / Probleme de chirurgie oncologica 2. Lectia japoneza. Limfadenectomia D2 în cancerul gastric.

At present there is accumulating evidence supporting the D2 lymphadenectomy in gastric cancer performed according the rules of the Japanese school of surgery. The D2 lymphadenectomy by open surgery seems to gain a wide acceptance and to become a standard therapy. The minimally invasive D2 lymphadenectomy (by laparoscopic or robotic surgery) in advanced gastric cancer showed promising results. However, these advanced minimally invasive techniques have still to be performed only in highly specialized surgical centers, with a large experience in oncological surgery. Further clinical trials are needed in order to verify the encouraging data of the few studies published until now in this field.

[Current problems in surgical oncology: 1. Theoretical models in oncology and their implications in surgical therapy]. / Probleme de chirurgie oncologica: 1. Modele teoretice în oncologie si implicatiile lor în tratamentul chirurgical.

Cancer biology has proven to be far more complex than imagined twenty years ago. While current treatment strategies (i.e., surgery, chemotherapy, and radiation) are successful in many cancers, they all have limitations. In some types of solid tumors some survival progress has been recorded, such in the case of breast and colorectal cancer, but these improvements are probably mainly due to screening programmes and earlier detection than to more-effective treatment. In other tumor types the mortality certainly increased: the death rate from lung cancer rose from 43 to 53 per 100,000 people from 1975 to 2005, the death rate from melanoma has risen nearly 30 percent, and death rate from liver and bile-duct cancer almost doubled, from 2.8 to 5.3 per 100,000. Cancer is commonly viewed as minimally controlled by modern medicine, especially when compared with other major diseases (Sharon Begley, 2008). Either directly from the phenomenological observation or through the biological model, mathematicians and biologists can generate mathematical models aimed at describing the biological phenomenon. The analysis of the solution properties by mathematical methods will give a description of the dynamics resulting in a deeper insight into the problem. The models can be implemented numerically to give rise to in silico models. The quality of the modeling process can be tested, validating the results of the simulations with experiments and clinical data. The theoretical predictions generated from the models may optimize the experimental protocol by identifying the most promising candidates for further clinical investigation. The speed with which large numbers of simulations can be performed may reduce the number of animal experiments and identify new experimental programmes and optimal cancer therapy schedules. However, it is clear that surgical decisions in cancer therapy are strongly driven by the theoretical hypotheses of local tumor evolution and malignant cells dissemination. For 60 years cancer was seen as a disease that arose in one location and spread through the lymphatic system first to nearby lymph nodes and subsequently to other organs. This theory of "contiguous" development of metastases has become known as the Virchow-Halsted theory. After 1954 an alternative theory was formulated by B. Fisher stating "that breast cancer is a systemic disease". Following the therapeutic implications of this "systemic theory," the disease has been attacked in recent years by chemotherapy and hormone therapy to the whole body. In 1994 S. Hellman stated the case for what he calls the "spectrum theory." He observed that there are intermediate tumor states between purely localized lesions and widely metastatic. Such clinical circumstances are not accounted for by either the contiguous (Halsted theory) or the systemic (systemic theory) hypotheses and supports the idea that loco-regional therapies (surgery and radiotherapy) may be useful in some cases. So, it is obvious that the extent and the role of cancer surgery are direct consequences of our theoretical understanding of cancer natural history. The genetical, pathological and clinical heterogeneity of cancers suggest new theoretical approaches based on chaos and fractal theory.

[MicroRNA's role in sepsis and endotoxin tolerance. More players on the stage]. / Rolul microRNA in sepsis. Noi actori in scenariul tolerantei la endotoxina.

MicroRNAs are non-coding RNA fragments, well characterized and well preserved along the evolution of the species and whose essential role is to regulate gene expression. MicroRNAs perform its action on messenger RNA ("target"). They induce degradation or repression of target translation with a significant decrease in the quantity and the activity of proteins. MicroRNAs are involved in normal cell function. Abnormal levels of microRNA were found in several pathological contiditions such as cancer, autoimmune diseases, viral infections, sepsis. Sepsis appears as a result of an improper inflammatory response after systemic bacterial infection. It remains a disease with a high incidence and mortality despite the evolution of diagnostic and treatment techniques. Sepsis patients have similar features to those found in the endotoxin tolerance phenomenon. Endotoxin tolerance is a state of hyporesponsivness to endotoxin challenge induced by a prior exposure. Due to its important role in repression of the pro-inflammatory cytokines translation, microRNA can be considered a new mechanism of endotoxin tolerance and a new mechanism involved in sepsis pathogenesis. In sepsis patients abnormal levels of the following types of microRNA were found: miR-146, miR-155, miR150, miR-132. Further studies are carried out to demonstrate the potential role of microRNA as biomarkers in sepsis.