Multidrug transporter MRP4/ABCC4 as a key determinant of pancreatic cancer aggressiveness.

Recent findings show that MRP4 is critical for pancreatic ductal adenocarcinoma (PDAC) cell proliferation. Nevertheless, the significance of MRP4 protein levels and function in PDAC progression is still unclear. The aim of this study was to determine the role of MRP4 in PDAC tumor aggressiveness. Bioinformatic studies revealed that PDAC samples show higher MRP4 transcript levels compared to normal adjacent pancreatic tissue and circulating tumor cells express higher levels of MRP4 than primary tumors. Also, high levels of MRP4 are typical of high-grade PDAC cell lines and associate with an epithelial-mesenchymal phenotype. Moreover, PDAC patients with high levels of MRP4 depict dysregulation of pathways associated with migration, chemotaxis and cell adhesion. Silencing MRP4 in PANC1 cells reduced tumorigenicity and tumor growth and impaired cell migration. Transcriptomic analysis revealed that MRP4 silencing alters PANC1 gene expression, mainly dysregulating pathways related to cell-to-cell interactions and focal adhesion. Contrarily, MRP4 overexpression significantly increased BxPC-3 growth rate, produced a switch in the expression of EMT markers, and enhanced experimental metastatic incidence. Altogether, our results indicate that MRP4 is associated with a more aggressive phenotype in PDAC, boosting pancreatic tumorigenesis and metastatic capacity, which could finally determine a fast tumor progression in PDAC patients.

Prospective randomized, blind comparison of ropivacaine and levobupivacaine for superficial plexus anesthesia in carotid endoarterectomy.

BACKGROUND: The authors performed a study to evaluate if the onset time, duration of sensory block, and quality of postoperative analgesia in superficial cervical plexus anesthesia with 0.5% levobupivacaine (1 mg/kg) was greater than 0.75% ropivacaine (1.5 mg/kg). DESIGN: randomized, double-blind study. SETTING: University teaching hospital. PARTICIPANTS: 28 consecutive patients undergoing elective carotid thromboendoarterectomy were randomized into two groups. INTERVENTIONS: patients received either 1 mg/kg of 0.5% levobupivacaine (N.=15), or 1.5 mg/kg of 0.75% ropivacaine (N.=13). We assessed the onset time (pinprick test), duration of sensory block, and postoperative analgesia with the two drugs. RESULTS: Onset time of sensory block was 20+/-6 min with ropivacaine and 29+/-8 min with levobupivacaine (P=0.003). Intraoperatively we used different total doses of lidocaine, with the median (interquartile range) dose of 50 (40-100) mg for ropivacaine and 130 (60-180) mg for levobupivacaine (P=0.05). The first pain medication was requested after 12+/-0.4 h by ropivacaine patients and after 11+/-1.6 h by levobupivacaine patients (P=0.5). CONCLUSION: No beneficial effect was noted in the quality of nerve block or patient's satisfaction for 0.5% levobupivacaine when compared to 0.75% ropivacaine.

Management of thoracoabdominal aortic aneurysms.

Conventional treatment of thoracoabdominal aortic aneurysms (TAAAs) consists of graft replacement with reattachment of the main aortic branches. Over the past 20 years a multimodal approach has gradually evolved to reduce the trauma of surgery by maximizing organ protection, allowing experienced surgical Centers to have better outcomes than previously reported. However, mortality and morbidity associated to TAAA open repair remain significant. Hybrid repair, consisting of open aortic debranching and revascularization followed by endovascular exclusion of the aneurysm, may extend the indications of TAAA repair to high-risk patients that cannot benefit from surgery, however results are still under evaluation. Aim of this paper is to illustrate the management and results of thoracoabdominal aortic aneurysms surgery with open techniques of organ protection and hybrid approach in our Center.

Carotid Endarterectomy: experience in 8743 cases.

INTRODUCTION: Recently published case series of patients undergoing carotid endarterectomy suggested a reduction in the rate of perioperative neurologic events when compared to those reported in the large randomized trials performed in the 1990s, without great differences between high and low risk patients. METHODS: As a major center of Vascular Surgery we prospectively collected data on 8743 carotid endarterectomy procedures (eversion technique 75%, patch closure 17.5%) performed in the period 1992-2009. RESULTS: Perioperative mortality was 0.32% (27/8743) with myocardial infarction being the most frequent cause (9 patients). Perioperative neurological morbidity was 1.04% (91/8743) with 51 major and 40 minor strokes. In 201 cases (2.3%) a cervical hematoma (suture-line bleeding in 41 cases and or diffuse oozing in 160 cases) in the early postoperative period necessitated urgent wound revision. In 262 (3.0%) cases we observed permanent or transient lesions of cranial nerves in the postoperative period. There was no significant difference in the combined ipsilateral stroke and perioperative death rate in octogenarian patients (2.1% in octogenarians and 1.2% in younger patients, p>0.05), even though an increasing trend was evident. CONCLUSIONS: Carotid endarterectomy has a reduced rate of perioperative complications when compared to those previously reported in literature. The low complication rate is related to improved preoperative patients evaluation, surgeons' increasing experience and to surgical and anesthesiological techniques. Carotid angioplasty and stenting should have their results compared to these real world results of carotid endarterectomy in order to asses their reliability when treating extracranial cerebrovascular disease.

Prospective, randomized, controlled evaluation of the preventive effects of positive end-expiratory pressure on patient oxygenation during one-lung ventilation.

BACKGROUND AND OBJECTIVE: This prospective, randomized, controlled study evaluated the effects on oxygenation by applying a selective and patient-specific value of positive end-expiratory pressure (PEEP) to the dependent lung during one-lung ventilation. METHODS: Fifty patients undergoing thoracic surgery under combined epidural/general anaesthesia were randomly allocated to receive zero PEEP (Group ZEEP, n = 22), or the preventive application of PEEP, optimized on the best thoracopulmonary compliance (Group PEEP, n = 28). Patients' lungs were mechanically ventilated with the same setting during two- and one-lung ventilation (FiO2 = 0.5; VT = 9mL kg(-1), inspiratory :expiratory time = 1 : 1, inspiratory pause = 10%). RESULTS: Lung-chest wall compliance decreased in both groups during one-lung ventilation, but patients of Group PEEP had 10% higher values than patients with no end-expiratory pressure (ZEEP) applied--Group ZEEP (P < 0.05). During closed chest one-lung ventilation, the PaO2 : FiO2 ratio was lower in Group PEEP (232 +/- 88) than in Group ZEEP (339 +/- 97) (P < 0.05); but no further differences were reported throughout the study. No differences were reported between the two groups in the need for 100% oxygen ventilation (10 patients of Group ZEEP (45%) and 14 patients of Group PEEP (50%) (P = 0.78)) or re-inflation of the operated lung during surgery (two patients of Group ZEEP (9%) and three patients of Group PEEP (10%) (P = 0.78)). Postanaesthesia care unit discharge required 48 min (25th-75th percentiles: 32-58 min) in Group PEEP and 45 min (30-57 min) in Group ZEEP (P = 0.60). CONCLUSIONS: The selective application of PEEP to the dependent, non-operated lung increases the lung-chest wall compliance during one-lung ventilation, but does not improve patient oxygenation.

[Respiratory exchange during laparoscopic and laparotomic cholecystectomy]. / Scambi respiratori durante colecistectomia laparoscopica e laparotomica.

The utility of laparoscopic cholecystectomy in reducing postoperative pain and patient's hospital discharge is already known. Nevertheless peritoneal gas insufflation required by surgical procedure can modify respiratory homeostasis during general anesthesia. The aim of this study was to evaluate the effect of laparoscopic cholecystectomy on pulmonary dead spaces and alveolar gas exchange during inhalation anesthesia compared with traditional laparotomic cholecystectomy. With the approval of Hospital Ethical Committee, thirty-one patients undergoing isoflurane general anesthesia for laparoscopic (CL-S, n = 16) and open (CL-T, n = 15) cholecystectomy were prospectively evaluated in order to asses modifications in physiological (VDphy/VT), anatomical (VDan/VT) and alveolar (VDalv/VT) dead space to tidal volume ratio, arterial to end-tidal carbon dioxide partial pressure difference [P(a-Et)CO2] and alveolar to arterial oxygen partial pressure difference (A-aDO2). Patients, 21-64 years-old, ASA I-II, had no cardiopulmonary diseases. The CL-S group required peritoneal insufflation of carbon dioxide with an intraabdominal pressure (IAP) of about 10-14 mmHg and antitrendelenburg positioning (15-20 degree). Expired gas measurements and arterial blood gas sample for pulmonary dead spaces and arterial to alveolar CO2 and O2 gradient calculation were performed 20 min after a steady state condition. VDphy/VT, VDalv/VT, P(a-Et)CO2 and A-aDO2 increased significantly in the CL-S compared to the CL-T group (p < 0.05). No differences were found in the VDan/VT. These results can be explained by analteration of the ventilation to perfusion ratio (VA/Q) with an increase of high VA/Q regions due to the antitrendelenburg positioning with a redistribution of blood flow towards basal zones.(ABSTRACT TRUNCATED AT 250 WORDS)

[Role of inhalation anesthetics in current anesthesiological practice]. / Ruolo degli anestetici per inalazione nella moderna tecnica anestesiologica.

Inhalational anesthetic agents represented for long time the sole or mainly anesthetic technique in general anesthesia. In the last twenty years, however, their use has been also related to toxicity among operating room personnel, chronically exposed to the volatile agents. This toxicity could induce the anesthesiologist to give up the volatile anesthetic agents in favour of a total intravenous anesthetic technique. Nevertheless well constructed prospective studies have clearly demonstrated that there is no significant correlation between morbidity index and chronic exposure to inhalational anesthetics. Furthermore a valid air exchange in the operating room, as well as more appropriate anesthesiologic procedures, have significantly reduced the concentration of volatile anesthetic agents in the operating areas. Nowadays inhalational anesthetic agents represent one of the different choices to perform general anesthesia. The anesthesiologist, however, according to patient's physical status and surgical procedure, must choose the anesthetic technique compatible with minimal risk both for patient and operating room personnel.