Prominent contribution of portal mesenchymal cells to liver fibrosis in ischemic and obstructive cholestatic injuries

Liver fibrosis is produced by myofibroblasts of different origins. In culture models, rat myofibroblasts derived from hepatic stellate cells (HSCs) and from periductal portal mesenchymal cells, show distinct proliferative and immunophenotypic evolutive profiles, in particular regarding desmin microfilament (overexpressed vs shut-down, respectively). Here, we examined the contributions of both cell types, in two rat models of cholestatic injury, arterial liver ischemia and bile duct ligation (BDL). Serum and (immuno)histochemical hepatic analyses were performed at different time points (2 days, 1, 2 and 6 weeks) after injury induction. Cholestatic liver injury, as attested by serum biochemical tests, was moderate/resolutive in ischemia vs severe and sustained in BDL. Spatio-temporal and morphometric analyses of cytokeratin-19 and Sirius red stainings showed that in both models, fibrosis accumulated around reactive bile ductules, with a significant correlation between the progression rates of fibrosis and of the ductular reaction (both higher in BDL). After 6 weeks, fibrosis was stabilized and did not exceed F2 (METAVIR) in arterial ischemia, whereas micronodular cirrhosis (F4) was established in BDL. Immuno-analyses of alpha-smooth muscle actin and desmin expression profiles showed that intralobular HSCs underwent early phenotypic changes marked by desmin overexpression in both models and that the accumulation of fibrosis coincided with that of alpha-SMA-labeled myofibroblasts around portal/septal ductular structures. With the exception of desmin-positive myofibroblasts located at the portal/septal-lobular interface at early stages, and of myofibroblastic HSCs detected together with fine lobular septa in BDL cirrhotic liver, the vast majority of myofibroblasts were desmin-negative. These findings suggest that both in resolutive and sustained cholestatic injury, fibrosis is produced by myofibroblasts that derive predominantly from portal/periportal mesenchymal cells. While HSCs massively undergo phenotypic changes marked by desmin overexpression, a minority fully converts into matrix-producing myofibroblasts, at sites, which however may be important in the healing process that circumscribes wounded hepatocytes.     

Positive end-expiratory pressure does not decrease cardiac output during laparoscopic liver surgery: A prospective observational evaluation

Background

Positive end-expiratory pressure (PEEP) has beneficial pulmonary effects but may worsen the hemodynamic repercussions induced by pneumoperitoneum (PNP) in patients undergoing laparoscopic liver resection. However, by increasing intraluminal vena cava (VC) pressures, PEEP may prevent PNP-induced VC collapse. The aim of this study was to test the validity of this hypothesis.

Less frequent catheter dressing changes decrease local cutaneous toxicity of high-dose chemotherapy in children,without increasing the rate of catheter-related infections: results of a randomised trial

Cutaneous lesions caused by catheter dressing changes can be serious and generate local pain in children undergoing high-dose chemotherapy followed by bone marrow transplantation. One hundred and thirteen children entered a randomised trial to compare two catheter dressing change frequencies (15 days vs 4 days). Skin toxicity was classified according to the following scale: grade 0: healthy skin, to grade 4: severe skin toxicity. A qualitative culture of the skin at the catheter entry site was taken whenever the dressing was changed. Of the 112 evaluable children (56 in each group) 32 developed grade > or = 2 local skin toxicity (eight in the 15-day group and 24 in the 4-day group; P = 0.001). Although higher in the 4-day group, the proportions of children experiencing pain during and between dressing changes were not statistically different between the two groups. The proportion of patients with one or more positive skin culture(s) at the catheter entry site during hospitalisation were similar in the two groups (27% in the 15-day group and 23% in the 4-day group) as were the proportions of documented nosocomial bloodstream infections (11% and 13%; NS). Whereas the planned frequency was maintained in the 4-day group (mean = 4 days, s.d. = 1), it was usually shortened in the 15-day group (mean = 8 days, s.d. = 4), mainly because dressings had loosened. Decreasing the catheter dressing change frequency proved efficient in reducing cutaneous toxicity without increasing the risk of local and systemic infection. In our unit, catheter dressings are changed every 8 days since this analysis.     

Continuous preperitoneal infusion of ropivacaine provides effective analgesia and accelerates recovery after colorectal surgery: a randomized, double-blind, placebo-controlled study

BACKGROUND: Blockade of parietal nociceptive afferents by the use of continuous wound infiltration with local anesthetics may be beneficial in a multimodal approach to postoperative pain management after major surgery. The role of continuous preperitoneal infusion of ropivacaine for pain relief and postoperative recovery after open colorectal resections was evaluated in a randomized, double-blinded, placebo-controlled trial. METHODS: After obtaining written informed consents, a multiholed wound catheter was placed by the surgeon in the preperitoneal space at the end of surgery in patients scheduled to undergo elective open colorectal resection by midline incision. They were thereafter randomly assigned to receive through the catheter either 0.2% ropivacaine (10-ml bolus followed by an infusion of 10 ml/h during 48 h) or the same protocol with 0.9% NaCl. In addition, all patients received patient-controlled intravenous morphine analgesia. RESULTS: Twenty-one patients were evaluated in each group. Compared with preperitoneal saline, ropivacaine infusion reduced morphine consumption during the first 72 h and improved pain relief at rest during 12 h and while coughing during 48 h. Sleep quality was also better during the first two postoperative nights. Time to recovery of bowel function (74 +/- 19 vs. 105 +/- 54 h; P = 0.02) and duration of hospital stay (115 +/- 25 vs. 147 +/- 53 h; P = 0.02) were significantly reduced in the ropivacaine group. Ropivacaine plasma concentrations remained below the level of toxicity. No side effects were observed. CONCLUSIONS: Continuous preperitoneal administration of 0.2% ropivacaine at 10 ml/h during 48 h after open colorectal resection reduced morphine consumption, improved pain relief, and accelerated postoperative recovery.     

Ischaemic cholestasis in intensive care unit

Cholestasis is frequently encountered in the ICU and is associated with a poor outcome. Ischaemia should be considered among the numerous aetiologic factors that may trigger cholestasis in the ICU. Blood supply to biliary tract is mainly provided by the hepatic artery, throughout a peribiliary vascular plexus. Interruption of the hepatic artery blood supply leads to cholestasis with a concomitant proliferative biliary reaction. Bile duct proliferation persists, while bile flow restores and biologic cholestasis syndrome spontaneously resolves in several weeks. Liver fibrosis related to the activation of periportal mesenchymental cells is observed in the close vicinity of proliferative bile ducts. Ischaemic cholestasis can be ascribed, at least partly, to hypoxia-induced disorders in the expression of hepatocytes biliary salts membrane transporters.     

La préhabilitation. Préparer les patients à la chirurgie pour améliorer la récupération fonctionnelle et réduire la morbidité postopératoire

Objective

Prehabilitation consists in providing a repetitive physical exercise before surgery to improve the postoperative recovery course. This review aims to evaluate the feasibility and the expected benefits of prehabilitation on the postoperative recovery course and the reduction of the postoperative morbidity.

Data sources

Data research has focused on English-language articles in the Medline database, published from 1989 to 2013. Keywords, used separately or in combination, were: prehabilitation, functional capacity, postoperative morbidity, physical activity.

Study selection

Selected articles were original articles, clinical cases, review articles and meta-analysis.

Data extraction

Articles were analyzed for feasibility, benefits and limitations of preoperative physical preparation techniques.

Data synthesis

Poor preoperative functional status is associated with increased postoperative morbidity. Elderly are more prone to postoperative complications. The improvement of preoperative physical status of these patients is possible and may reduce morbidity and allow faster recovery after major surgery. In order to improve efficiency, the training program must provide endurance and muscle reinforcement exercises, whose intensity must be adapted to the patient's baseline physical abilities. An average of three sessions per week over a period of six to eight weeks before surgery seemed a good compromise between feasibility and effectiveness.

Conclusion

The effectiveness of prehabilitation has been demonstrated in cardiovascular surgery and probably in abdominal surgery. Prehabilitation must be integrated into the overall patient medical management, and must be associated with preoperative refeeding and postoperative rehabilitation protocols. By optimizing all stages of the surgical patient management, from diagnosis to recovery, prognosis of high-risk surgical patients could be improved.     

Adaptative bile duct proliferative response in experimental bile duct ischemia

BACKGROUND/AIMS: A rat model of bile duct ischemia was established and used to examine the potential of bile duct proliferation to provide an adaptative response in cholestatic disorders. METHODS: Rats underwent partial or complete arterial deprivation of the liver. Serum biochemical tests, histological analyses and bile secretion measurements were performed at different time points up to 6 weeks after surgery. RESULTS: Rats developed biochemical signs of cholestasis exclusively after complete arterial deprivation. Within 4h, cholangiocytes in these rats showed morphological signs of cell damage. After 48h, they displayed VEGF expression and became proliferative. The proportion of Ki67-labeled cholangiocytes ( approximately 30%) was similar in interlobular bile ducts and periportal ductules. A ductular reaction made of well-formed bile ducts confined to portal tracts developed within 1 week. Bile flow which was initially decreased, was restored at 3 weeks, while the biochemical signs of cholestasis completely resolved at 6 weeks. At this time, the number of bile duct sections was maximal. Fibrosis intensity was also maximal, although moderate (相似文献   

Acute desflurane or sevoflurane exposure on a previously stabilized atracurium-induced neuromuscular block

BACKGROUND AND OBJECTIVE: The aim of this prospective study was to compare the effect of the administration of desflurane or sevoflurane to a fixed neuromuscular block. METHODS: After written consent, 12 patients were anaesthetized with propofol and sufentanil. Atracurium was administered via a continuous infusion in order to obtain 85% twitch depression of the control value assessed by repeated accelerometric stimulation at the adductor pollicis. Once stabilized over the course of 30 min, propofol was discontinued and either desflurane (n = 6) or sevoflurane (n = 6) was delivered at 1 MAC in a mixture of 50% O(2) in air. Study parameters were the magnitude and the time of twitch height variations. Results are presented in mean +/- SD. RESULT: Exposure to halogenated agents led to a significant reduction in twitch height with similar magnitude between the two agents. However, interaction with desflurane showed an initial and transient rise (35 +/- 22%) in twitch height before subsequent depression occurred. The time to reach 50% of the signal depression in the desflurane group was significantly delayed (25 +/- 7 vs. 11 +/- 4 min in the sevoflurane group; P < 0.01). CONCLUSIONS: On a stable neuromuscular block elicited by continuous infusion of atracurium, the abrupt administration of desflurane or sevoflurane reduces the accelerometric responses of the adductor pollicis in a similar way. This potentiating effect is produced faster after sevoflurane than after desflurane. With desflurane, a biphasic effect (of a transient and moderate increase followed by depression of the signal) was recorded.