Target fishing reveals PfPYK-1 and PfRab6 as potential targets of an antiplasmodial 4-anilino-2-trichloromethylquinazoline hit compound.

We present investigations about the mechanism of action of a previously reported 4-anilino-2-trichloromethylquinazoline antiplasmodial hit-compound (Hit A), which did not share a common mechanism of action with established commercial antimalarials and presented a stage-specific effect on the erythrocytic cycle of P. falciparum at 8 < t < 16 h. The target of Hit A was searched by immobilising the molecule on a solid support via a linker and performing affinity chromatography on a plasmodial lysate. Several anchoring positions of the linker (6,7 and 3') and PEG-type linkers were assessed, to obtain a linked-hit molecule displaying in vitro antiplasmodial activity similar to that of unmodified Hit A. This allowed us to identify the PfPYK-1 kinase and the PfRab6 GTP-ase as potential targets of Hit A.

Preventing the contamination of hospital personnel by cytotoxic agents: evaluation and training of the para-professional healthcare workers in oncology units.

This study was specifically focused on para-professional healthcare workers (PHCWs) who handle cytotoxic drugs and contaminated wastes at the Public Teaching Hospitals of Marseille (AP-HM), France. It first aimed at evaluating the knowledge and professional practice of the PHCWs who belong to a personnel category among the less informed and protected in hospitals. In a second time, this study also proposed to raise awareness, educate and train the staff on protective measures to minimise the exposure of the PHCWs to the potential toxicity of anticancer chemotherapy agents (or metabolites) when cleaning and handling both cytotoxic drugs and wastes. Among the 11 oncology units evaluated, 82% completed an assessment survey, 63% of which were PHCWs. Out of nine oncology units assessed, 89% reported limited knowledge of the general risk and of the safe handling of cytotoxic drugs, 89% reported using vinyl gloves which are the less protective ones. Forty-four per cent of the units used wet sweeping techniques for cleaning the floors, and 11% of the units did not have specific procedures for cleaning the equipments used for collecting contaminated excreta. Protective outer apparel was not always worn and chemotherapy wastes were not managed consistently between all units. Standardized procedures and guidelines to prevent occupational exposure were not used by PHCWs. More education and training are needed to improve safety.

[Observational study on outpatient sleeve gastrectomy]. / Chirurgie bariatrique en ambulatoire: étude observationnelle à propos de 68 sleeve gastrectomies.

UNLABELLED: The development of outpatient surgery is one of the major goals of the public health policy in 2010. The purpose of this observational study is to evaluate the feasibility of the laparoscopic sleeve gastrectomy (LSG) in ambulatory. METHODS: This prospective observational study was conducted from May 2011 to June 2013. The procedure was proposed for patients undergoing LSG who were predetermined inclusion criteria. Following preoxygenation, anaesthesia was induced with propofol and sufentanil. Tracheal intubation was facilitated with rocuronium. Anaesthesia was maintained with desflurane and remifentanil target-controlled infusion. Antiemetic prophylaxis was supplied with intravenous (IV) droperidol and dexamethasone; postoperative pain prophylaxis was IV paracetamol, nefopam, tramadol, and ropivacaine infiltration. The patients were extubated in the operating room and kept in the postoperative care unit. A water-soluble contrast examination was performed in the output of the postoperative care unit. Oral feeding was resumed immediately in the absence of fistula on this leak test in an ambulatory surgical unit. When the patient has satisfied the modified Post-Anaesthesia Discharge Scoring System (PADSS) criteria, he or she can then be discharged and sent home. RESULTS: Among 280 patients operated on for obesity by laparoscopic sleeve gastrectomy during the study period, 68 (24.2 %) underwent ambulatory procedure. Of the 68 obese patients, 94.1 % were female. Mean age was 34.4 years (22-55). Mean preoperative BMI was 42.6kg/m(2). Thirteen patients (19.1 %) had HTN; 7 (10.2 %) had dyslipidemia and 6 (8.8 %) had diabetes not requiring treatment. The mean operating time was 60minutes (range, 45-95) and there were no conversions to open surgery. No intra-operative anesthetic or surgical complications occurred. Mean time in the recovery room was 86.5minutes (35-240). The overall satisfaction rate was 92.6 % (n=63). No patients were admitted because of nausea or inadequate pain control. There were no re-admissions or hospitalizations were reported. We recorded five surgical complications including two case of gastric fistula, one case of gastric stenosis, one case of scar dehiscence and one case of splenic upper pole ischemia. Its complications have arisen from the fourth postoperative day. This does not undermine the ambulatory procedure. CONCLUSION: The laparoscopic sleeve gastrectomy in ambulatory is feasible with a dedicated anesthesiological concept in an expert surgical team. Appropriate patient selection is important in order to secure safety and quality of care within outpatient program. The risk versus benefit must be adequately evaluated on an individual basis.

Laparoscopic sleeve gastrectomy: imaging of normal anatomic features and postoperative gastrointestinal complications.

Morbid obesity is a public health problem in the United States and Europe and its prevalence is on the increase. Despite certain progress the efficacy of medical treatment remains limited. Bariatric surgery has consequently become an effective alternative for patients with morbid obesity. The bariatric operations most frequently performed are laparoscopic adjustable gastric banding (LAGB) and Roux-en-Y gastric bypass (LGB), but laparoscopic sleeve gastrectomy (LSG) is increasingly popular with both bariatric surgeons and patients due to its simplicity, rapidity and decreased morbidity. The purpose of this pictorial essay is to familiarize radiologists with the normal postoperative anatomic features and the imaging findings of postoperative gastrointestinal complications of laparoscopic sleeve gastrectomy because little literature exists on this subject.

Ventral hernia repair in a potentially septic milieu.

Repair of the abdominal wall is the last stage of abdominal surgery; pariet complications, particularly infection, can have serious impact on operative results. While abdominal wound infections are not universally preventable, they are often predictable; the aphorism of Jean Rives (Stoppa, 1999 [1]) summarizes this sequence: "Infection is the mother of postoperative incisional hernia and infection of the incisional hernia repair is the grand-daughter". Repair of the abdominal wall in a potentially septic milieu requires the solution of an equation involving four variables: mechanism of sepsis, its severity, the surgical approach, and choice of prosthetic material. These interdependent variables potentiate each other, requiring adaptations of surgical strategy that cannot be absolutely determined pre-operatively, even with collegial consultation.

Efficiency of laparoscopic sleeve gastrectomy on metabolic syndrome disorders: two years results.

OBJECTIVES: There are very few studies evaluating the efficacy of sleeve gastrectomy on the metabolic syndrome, truly a worldwide pandemic. The main objective of this study was to retrospectively determine the evolution of the metabolic syndrome and its associated comorbidities (type 2 diabetes, arterial hypertension, and dyslipidemia) at 24 months after sleeve gastrectomy. The secondary objective was to determine the predictive factors for resolution of this syndrome. MATERIAL AND METHODS: Between July 2004 and February 2008, 241 patients with morbid obesity (males: 17%) underwent sleeve gastrectomy in our center. Patients were seen in combined medical and surgical outpatient postoperative follow-up consultation at 3, 6, 12 and 24 months. Patients were classed as responders or not, according to whether or not the metabolic syndrome (as defined according to the National Cholesterol Education Program-Adult Treatment Panel III [NCEP-ATPIII]) disappeared at 24 months follow-up. RESULTS: Thirty-six patients (15% of all patients, 30% of males) presented initially with metabolic syndrome. Twenty-six patients (72%) still had metabolic syndrome at 6 months, 17 patients (47%) at 12 months, and 13 patients (36%) at 24 months. The main parameters that regressed after sleeve gastrectomy were type 2 diabetes and hypertriglyceridemia. In univariate analysis, only one parameter (systolic blood pressure) appeared to be a factor of non-resolution of the metabolic syndrome at 24 months. CONCLUSION: Our study showed that sleeve gastrectomy reduced the incidence of the metabolic syndrome and several of its components.

Partial removal of infected parietal meshes is a safe procedure.

INTRODUCTION: Open tension-free hernioplasty using prosthetic meshes dramatically reduced recurrence rates after hernia or incisional hernia repair and has become the rule. Mesh infections (MI) are the major complication of prosthetic material. The aim of this study was to assess the efficacy of partial removal of mesh (PRM) therapy in the treatment of MI. MATERIALS AND METHODS: From January 2000 to April 2010, from a prospective database, we retrospectively selected patients who underwent surgery for MI. We studied the epidemiological data (sex, age, obesity, diabetes, smoking), the operating time of the initial intervention, the presence of intestinal injuries during the first intervention, the average interval between initial surgical procedure and MI, the location of the hernia, the average size of the hernia, type of mesh used, the position of the mesh, type of surgery performed, the number through interventions required to achieve a cure, the cumulative duration of hospital stay and hernia recurrence rates. RESULTS: Twenty-five patients were supported for a MI in our institution. There were 9 women (36 %) and 16 men (64 %). The median age was 59 years (range 37-78). There were 4 inguinal hernias (16 %), 15 incisional hernias (60 %) and 6 multirecurrent incisional hernias (24 %). It was performed a PRM in 92 % of cases (n = 23), a total excision of the prosthesis in 4 % of cases (n = 1) and no removal of prosthesis in 4 % of cases (n = 1). The average number of reoperations before healing was 1 (range 1-5). The mean cumulative duration of hospitalization until healing was 9.5 days (range 2-43). No visceral resection was performed. CONCLUSION: PRM is feasible in most cases allowing first to spare the capital parietal patients and secondly to avoid major surgery. In case of failure, total removal of the mesh can be discussed.

Is there a place for pigtail drains in the management of gastric leaks after laparoscopic sleeve gastrectomy?

Laparoscopic sleeve gastrectomy (LSG) has a specific morbidity profile in which gastric leak (GL) is the main complication. With a view to defining a standardized protocol for GL management, the present retrospective study sought to describe the clinical patterns of post-LSG GL and treatment of the latter in our university medical center. From July 2004 to December 2010, 25 patients were included. GL was described in terms of clinical presentation, time to onset, and location in the staple line. Treatment of GL with pharmacologic, radiologic, endoscopic, and/or surgical procedures was always validated by a multidisciplinary care team. "Treatment success" was defined as the absence of contrast agent leakage on CT and endoscopy after removal of covered metallic stent or pigtail drains. Systemic inflammation and peritonitis were the main signs for early-onset GL (56%), whereas pulmonary symptoms and intra-abdominal abscesses revealed delayed-onset GL (44%). Surgery was always performed for early-onset GL. In the total study population, the median number of endoscopic procedures was five (range, 1-11) per patient, of covered SEMS was three (range, 1-8), and of pigtail drains was three (range, 1-4). Nine (36%) patients presented endoscopic-related complications. Four (16%) patients with treatment failure underwent radical surgery. The mortality rate was 4% (n = 1). The management of post-LSG GL is challenging. Surgery was always performed for early-onset GL, whereas treatment of delayed-onset GL was based on endoscopy. Pigtail drains required fewer procedures per patient, were better tolerated, and had lower morbidity-mortality than covered SEMS.

Progressive preoperative pneumoperitoneum preparation (the Goni Moreno protocol) prior to large incisional hernia surgery: volumetric, respiratory and clinical impacts. A prospective study.

INTRODUCTION: Progressive preoperative pneumoperitoneum (PPP) is used to prepare incisional hernias with loss of domain (IHLD) operations. The aim of the present study was to analyze the effect of PPP on peritoneal volume [measured using a new computed tomography (CT)-based method] and respiratory function. METHODS: From July 2004 to July 2008, 19 patients were included in a prospective, observational study. The volumes of the incisional hernia (VIH), the abdominal cavity (VAC), the total peritoneal content (VP) and the VIH/VP ratio were measured before and after PPP using abdominal CT scan data. Spirometric parameters were measured before and after PPP, and postoperative clinical data were evaluated. RESULTS: Before and after PPP, the mean VIH was 1,420 cc and 2,110 cc (P  < 0.01), and the mean VAC was 9,083 cc and 11,104 cc (P < 0.01). The VAC increased by 2,021 cc (P < 0.01) and was greater than the mean VIH before PPP. After PPP, the spirometric measurements revealed a restrictive syndrome. The overall postoperative morbidity rate was 37%. CONCLUSIONS: PPP increased the hernia and abdominal volumes. PPP induced a progressive, restrictive syndrome.

Stapling and Section of the Nasogastric Tube during Sleeve Gastrectomy: How to Prevent and Recover?

Bariatric surgery has become an integral part of morbid obesity treatment with well-defined indications. Some complications, specific or not, due to laparoscopic sleeve gastrectomy (LSG) procedure have recently been described. We report a rare complication unpublished to date: a nasogastric section during great gastric curve stapling. A 44-year-old woman suffered of severe obesity (BMI 36.6 kg/m2) with failure of medical treatments for years. According to already published technique, a LSG was performed. Six hours postoperatively, a nurse removed the nasogastric tube according to the local protocol and the nasogastric tube was abnormally short, with staples at its extremity. Surgery was performed with peroperative endoscopy. In conclusion, this is the first publication of a nasogastric section during LSG. Therefore we report this case and propose a solution to prevent its occurrence. To avoid this kind of accident, we now systematically insert the nasogastric tube by mouth through a Guedel cannula. Then, to insert the calibrating bougie, we entirely withdraw the nasogastric tube.

Albumin-bound paclitaxel: the benefit of this new formulation in the treatment of various cancers.

Paclitaxel and docetaxel are established as the standards of care, either as monotherapy or in combination with other cytotoxic agents in metastasic breast cancer. In order to improve the efficiency of solvent-based paclitaxel and to overcome its drawbacks in terms of safety, a solvent-free formulation has been developed. This work is a review of the albumin-bound paclitaxel data relative to its pharmacodynamic and pharmacokinetic profiles, its therapeutic efficiency and its safety of use. The activity of albumin-bound paclitaxel in phase II and III trials indicates its significant clinical efficiency in the treatment of metastatic breast cancer. In lung and pancreatic cancer and in melanoma, the use of albumin-bound paclitaxel leads to interesting results which require further investigations. Preclinical and clinical studies have shown that albumin-bound paclitaxel is associated with a better tolerance compared to standard paclitaxel.

Peritoneal volume is predictive of tension-free fascia closure of large incisional hernias with loss of domain: a prospective study.

INTRODUCTION: The surgical treatment of large incisional hernias with loss of domain (LIHLD) carries the risk of fascia closure under tension and, thus, abdominal compartment syndrome. We investigated volume measurements as a predictive factor for tension-free fascia closure. PATIENTS AND METHODS: From September 2004 to July 2008, we prospectively included 17 patients with LIHLD. The operation was prepared by a progressive preoperative pneumoperitoneum (PPP) technique known as the Goni Moreno procedure. The patient's age and body mass index (BMI), the incisional hernia's width, length and surface area, and the incisional hernia volume (IHV)/peritoneal volume (PV) ratio <20% were evaluated as predictive factors for tension-free fascia closure. A tension-free closure was defined as a closure in which the use of a surgical device for avoiding postoperative compartment syndrome was not required. RESULTS: The mean PPP volume introduced was 12.7 ± 4.4 l (range 4.5-19.2) over a period of 11 ± 6 days (range 4-24). The mean width, height and surface area of the incisional hernia after PPP were 11.3 ± 4.7 cm (range 4.5-19), 13.4 ± 7.8 cm (range 4.4-30) and 165 ± 101 cm(2) (range 19-304), respectively. The mean IHV after PPP was 2,374 ± 1,356 cc (range 517-4,802) and the mean abdominal cavity volume was 9,558 ± 4,106 cc (range 4,785-21,782). The mean IHV/PV ratio was 16.3 ± 10.4% (range 4.4-34). In a univariate analysis, the BMI and the IHV/PV ratio were predictive of tension-free fascia closure. In a multivariate analysis, only an IHV/PV ratio <20% was a significant predictive factor. CONCLUSIONS: The IHV/PV ratio is predictive of tension-free fascia closure for hernias or incisional hernias with loss of domain. Simplification of the volumetry method is necessary.

[Intrauterine fetal death in a woman with a gastric banding]. / Mort fœtale in utero chez une femme porteuse d'un anneau gastrique.

Obesity defined by a Body Mass Index (BMI) over 30 is a major public health problem. Its correction may require surgical treatment in case of failure of adequate medical care. A pregnancy achieved in the aftermath of this surgery must be planned and monitored as a high-risk pregnancy, in fact it can complicate. We report here the occurrence of fetal death in a patient with a gastric banding.

[Late complications from abdominal wall surgery: report of three cases of mesh migration into hollow viscus]. / Complications tardives de la chirurgie pariétale abdominale: à propos de trois cas de migration de prothèse dans un organe creux.

Laparoscopic mesh repair of ventral abdominal wall hernias is routinely performed. Mesh detachment and migration within the abdominal cavity is a late complication of this procedure. Symptoms are non-specific and imaging diagnosis is difficult to achieve because this complication is rare and overlooked.

[Longitudinal sleeve gastrectomy as a stand-alone bariatric procedure: Results of a multicenter retrospective study]. / La gastrectomie longitudinale (sleeve gastrectomy) comme unique chirurgie bariatrique : résultats d'une étude rétrospective multicentrique de 446 patients.

INTRODUCTION: Sleeve gastrectomy as an isolated procedure is a new option in bariatric surgery. The aim of this study was to evaluate its short and medium term (2 years) results in a multicenter setting. MATERIALS: This is a retrospective study including 446 patients undergoing surgery in 14 teaching, private, and public hospitals. RESULTS: The immediate post-operative course were uneventful in 83.3% of patients. Minor complications occurred in 10.9% of patients and major complications in 5.3%. Suture line leaks occurred in 4.3% of the whole series. There was no mortality and the rate of reoperation was 2%. Overall mean weight loss after two years was 32 kg and the mean excess weight loss was 62%. Weight loss was significantly greater in non super-obese patients (p=0.0003). CONCLUSIONS: This study confirms the feasibility of sleeve gastrectomy in a multicenter setting; it is efficacious at two years as an isolated bariatric procedure for non super-obese patients. It is possible that an additional second-stage procedure may be necessary for super-obese patients.