Fabrizio Bresadola

Preemptive analgesia : Intraperitoneal local anesthetic in laparoscopic cholecystectomy : A randomized, double-blind, placebo-controlled study

Background A controversy exists over the effectiveness and clinical value of preemptive analgesia. Additional studies are needed to define the optimum intensity, duration, and timing of analgesia relative to incision and surgery. Methods One hundred twenty patients undergoing laparoscopic cholecystectomy under general anesthesia plus topical peritoneal local anesthetic or saline were studied. Local anesthetic (0.5% bupivacaine with epinephrine) or placebo solutions were given as follows: immediately after the creation of a pneumoperitoneum (blocking before surgery), and at the end of the operation (blocking after surgery). Patients were randomly assigned to one of four groups of 30 patients each. Group A (placebo) received 20 ml 0.9% saline both before and after surgery, group B received 20 ml 0.9% saline before surgery and 20 ml local anesthetic after surgery, group C received 20 ml local anesthetic both before and after surgery, group P received 20 ml local anesthetic before and 20 ml 0.9% saline after surgery. Pain was assessed using a visual analog scale and a verbal rating scale at 0, 4, 8, 12, and 24 h after surgery. Metabolic endocrine responses (blood glucose and cortisol concentrations) and analgesic requirements also were investigated. Results Pain intensity (visual analog and verbal rating scales) and analgesic requirements were significantly less in the group receiving bupivacaine after surgery compared to placebo. However, in the groups receiving bupivacaine before surgery, both pain intensity and analgesic consumption were less than in the group receiving bupivacaine only after surgery. Blood glucose and cortisol concentrations 3 h after surgery were significantly less in groups receiving bupivacaine before surgery. Conclusions The results indicate that intraperitoneal local anesthetic blockade administered before or after surgery preempts postoperative pain relative to an untreated placebo-control condition. However, the timing of administration is also important in that postoperative pain intensity and analgesic consumption are both lower among patients treated with local anesthetic before versus after surgery.

Elective transumbilical compared with standard laparoscopic cholecystectomy.

OBJECTIVE To compare the transumbilical technique of laparoscopic cholecystectomy with standard laparoscopic cholecystectomy. DESIGN Randomised open study. SETTING Teaching hospital, Italy. SUBJECTS 90 patients who required elective cholecystectomy under general anaesthesia. INTERVENTIONS Standard laparoscopic cholecystectomy through 4 ports or transumbilical cholecystectomy through 2 ports. MAIN OUTCOME MEASURES Amount of pain and analgesia, cost, side effects, and cosmesis. RESULTS 25 patients were excluded from analysis (8 in the standard group because relevant data were not recorded; and 17 in the transumbilical group in 4 of whom relevant data were not recorded, and 13 for technical reasons). 32 patients who had standard, and 25 who had transumbilical cholecystectomy had operative cholangiograms. There were no complications, no side effects, and no conversions to open cholecystectomy. Those who had transumbilical cholecystectomy had significantly lower pain scores (p<0.05) and required significantly less analgesia during the first 24 hours (p<0.05) than those who had standard laparoscopic cholecystectomy. CONCLUSION Once the learning curve has been completed, transumbilical cholecystectomy is possible without some of difficulties associated with standard laparoscopic cholecystectomy.

Laparoscopic vs open splenectomy in the management of hematologic diseases.

AbstractBackground: Laparoscopic splenectomy (LS) is becoming the gold standard in the treatment of several splenic diseases. Shorter postoperative stay and more rapid return to full activity are the primary advantages of LS. Methods: Prospective data collection of 44 consecutive LS (group 1) and comparison with a historical control group of 56 consecutive open splenectomies (OS) (group 2) were performed for hematologic diseases. Results: The LS patients started earlier on an oral diet (p < 0.0001) and left the hospital sooner (p < 0.0002) than OS patients. Less blood transfusion (p < 0.004) and pain medication (p < 0.0001) was required by LS patients. They also had fewer postoperative complications (p < 0.03). Compared by diagnosis, patients with laparoscopic idiopathic thrombocytopenic purpura or Hodgkins disease started to eat earlier (p < 0.0001) and left the hospital sooner (p < 0.01). Multivariate analysis showed that time to oral diet and postoperative stay was related to operative technique and age. Morbidity and pain medications were related, respectively, to transfusion requirements and type of surgical approach. Conclusions: Used to manage hematologic diseases, LS is feasible, effective, and safe. It offers several advantages over the open approach. The type of surgical approach seems to be the crucial factor in determining the length of the postoperative course.

Mobilization of Bone Marrow-Derived Hematopoietic and Endothelial Stem Cells After Orthotopic Liver Transplantation and Liver Resection

In animals, the bone marrow (BM) is a source of liver‐repopulating cells with therapeutic potential in case of tissue damage. However, the early response of human BM‐derived stem cells (SC) to liver injury is still unknown. Here, we studied 24 patients undergoing orthotopic liver transplantation (OLT) for end‐stage liver disease or hepatocellularcarcinoma, and 13 patients submitted to liver resection. The concentration of circulating BM‐derived SC was determined by phenotypic analysis and clonogenic assays. Moreover, we assessed the serum level of inflammatory and tissue‐specific cytokines. Reverse transcriptase‐polymerase chain reaction and fluorescence‐in situ hybridization were also used to characterize mobilized SC. At baseline, patients showed a significant lower concentration of circulating CD133+, CD34+ SC and clonogenic progenitors (colony‐forming unit cells) than healthy controls. However, the time‐course evaluation of peripheral blood cells after OLT demonstrated the significant early mobilization of multiple subsets of hematopoietic and endothelial stem/progenitor cells. Cytogenetic and molecular analyses of CD34+ cells showed the host origin of mobilized SC and the expression of transcripts for GATA‐4, cytokeratin 19, and α‐fetoprotein hepatocyte markers. In contrast with OLT, only total circulating CD34+ cells significantly increased after liver resection. Mobilization of BM cells after OLT or liver surgery was associated with increased serum levels of granulocyte‐colony stimulating factor, interleukin‐6, stem cell factor, hepatocyte growth factor, and vascular endothelial growth factor. In summary, we demonstrate that tissue damage after OLT and liver resection induces increased serum levels of multiple cytokines but only ischemia/reperfusion injury associated with OLT results in the remarkable mobilization of BM stem/progenitor cells.

Incidental pancreatic cysts on 3D turbo spin echo magnetic resonance cholangiopancreatography: prevalence and relation with clinical and imaging features

PurposeTo estimate the prevalence of incidental pancreatic cysts (IPCs) in asymptomatic patients addressed to magnetic resonance cholangiopancreatography (MRCP), and to correlate it with clinical and imaging features.Materials and methodsMagnetic resonance cholangiopancreatography performed over 26-months on 152 patients with unsuspected/unknown pancreatic disease were reviewed to assess IPCs’ features of presentation. Multivariate analysis was performed to evaluate the correlation of IPCs with clinical information and type of pancreaticobiliary findings at MRCP.ResultsPrevalence of IPCs was 44.7%. Cysts sized 3–24 mm (mean, 6.08 mm), and were ≤4 in number in 83.8% of patients. Based on number, dimensions and relation with the main pancreatic duct, IPCs presented with intraductal-papillary-mucinous neoplasm (IPMN)-like or indeterminate patterns in 31.7% and 13.1% of patients, respectively. At follow-up on 24 patients, no evolution was found, except in one patient with proven IPMN showing increase in cysts number and dimensions (evolution rate of 4.1%). Features correlating with IPCs were age ≥60 years old, and history of autoimmune hepatobiliary disease, showing odds ratios of 5.95 (95% CI 2.77–12.79) and 0.13 (95% CI 0.04–0.44), respectively.ConclusionsIncidental pancreatic cysts represent a frequent finding at MRCP, correlating positively with increasing age, and negatively with biliary autoimmune disease. Cysts more frequently present with IPMN-like pattern.

Hyperlactacidemia Potentially Due to Linezolid Overexposure in a Liver Transplant Recipient

Sir—A 59-year-old white liver transplant recipient developed bilateral pneumonia on day 4 after the operation. After performing bronchoscopy with bronchoalveolar lavage, empirical therapy with piperacillin-tazobactam (4.5 g every 6 h) and levofloxacin (500 mg every 12 h) was commenced. During the subsequent 24 h, the patient’s clinical condition worsened until he developed severe sepsis. Drotrecogin-a was administered, but because of the persistence of the patient’s critical condition, and because no bacteria were isolated, antibiotic therapy was shifted 48 h later to meropenem (500 mg every 6 h) plus linezolid (600 mg every 12 h). Over the subsequent days, the patient’s clinical condition slowly improved. However, despite there being no evidence of graft dysfunction or renal failure, a progressive asymptomatic increase in the plasma lactate level was noted (peak level, 8.4 mmol/L) (figure 1). On day 10 of the second-line antibiotic regimen, therapy was de-escalated by withdrawing meropenem. In accordance with our institution’s antibiotic policy, which is oriented at optimizing therapy for critically ill patients [1], multiple blood samples were obtained to assess linezolid exposure during a dosing interval and were subsequentlyanalyzed by high-performance liquid chromatography [2]. Pharmacokinetic analysis revealed significant plasma overexposure to linezolid (12-h area under the curve, 412.55 /L; maximum concentration, 43.32 mg h mg/L; minimum concentration, 26.99 mg/ L) because of impaired clearance (1.51 L/ h) with a prolonged elimination half-life (16.57 h) [3]. We hypothesized that the patient potentially had drug-induced hyperlactacidemia. On day 12 of hospitalization, linezolid was withdrawn, and blood samples were obtained to determine whether plasma drug levels were decreasing. During the subsequent 2 days, concomitantly with a decrease in the plasma linezolid level, a progressive decrease of the plasma lactate level (until complete normalization occurred) was documented (figure 1). Hyperlacticidemia during linezolid therapy has been previously reported to be an adverse event that mainly develops after long treatment periods and that slowly resolves after withdrawal of the drug [4–6]. Conversely, in the case we report, lactate levels started increasing just after the first week of treatment, rapidly achieved the maximum level, and returned to a normal level within 48 h after drug withdrawal. It has been suggested that, on the basis of its mechanism of action, linezolid may cause hyperlacticidemia by inhibiting mitochondrial protein synthesis [6]. Therefore, hyperlacticidemia should be expected to occur earlier in the course of treatment and to be more severe in patients who

Portal vein thrombosis after intraportal hepatocytes transplantation in a liver transplant recipient

Hepatocytes transplantation is viewed as a possible alternative or as a bridge therapy to liver transplantation for patients affected by acute or chronic liver disorders. Very few data regarding complications of hepatocytes transplantation is available from the literature. Herein we report for the first time a case of portal vein thrombosis after intraportal hepatocytes transplantation in a liver transplant recipient. A patient affected by acute graft dysfunction, not eligible for retransplantation, underwent intraportal infusion of 2 billion viable cryopreserved ABO identical human allogenic hepatocytes over a period of 5 h. Hepatocytes were transplanted at a concentration of 14 million/ml for a total infused volume of 280 ml. Doppler portal vein ultrasound and intraportal pressure were monitored during cell infusion. The procedure was complicated, 8 h after termination, by the development of portal vein thrombosis with liver failure and death of the patient. Autopsy showed occlusive thrombosis of the intrahepatic portal vein branches; cells or large aggregates of epithelial elements (polyclonal CEA positive), suggestive for transplanted hepatocytes, were co‐localized inside the thrombus.

Laparoscopic versus open splenectomy in the management of splenomegaly: Our preliminary experience

BACKGROUND Laparoscopic splenectomy for normal-sized spleens has several advantages compared with laparotomy. Only a few cases of splenomegaly done by laparoscopy are reported in the literature. The purpose of this study is to show that laparoscopy for splenomegaly is feasible and has several advantages over the open operation. METHODS We performed retrospective chart review of 8 cases of splenomegaly managed by laparoscopy (group 1), 15 cases of open splenomegaly (group 2), and 27 cases of laparoscopic splenectomy for normal-sized spleens (group 3). Comparison has been done between groups 1 and 2 and groups 1 and 3 in terms of operative time, intraoperative estimated blood loss, need for blood transfusion, postoperative ileus, postoperative stay, and mortality and morbidity rates. RESULTS Patients in group 1 required longer operative time and significantly less intraoperative blood transfusion compared with group 2. The postoperative course was less complicated and shorter in group 1 than in group 2. Operative time was longer in group 1 compared with group 3. No significant differences in terms of postoperative course have been found between groups 1 and 3. CONCLUSIONS Laparoscopy for splenomegaly is a feasible, effective, and safe technique for experienced laparoscopic surgeons. This approach seems to have several advantages over the open operation. Prospective, randomized trials would be required for a proper quantitative evaluation.

Superiority of transplantation versus resection for the treatment of small hepatocellular carcinoma

The best therapy for hepatocellular carcinoma (HCC) is still debated. Hepatic resection (HR) is the treatment of choice for single HCC in Child A patients, whereas liver transplantation (LT) is usually reserved for Child B and C patients with single or multiple nodules. The aim of this study was to compare HR and LT for HCC within the Milan criteria on an intention‐to‐treat basis. Forty‐eight patients were treated by LT and 38 by HR. The median time on the waiting list for transplantation was 118 days. The estimated overall survival was significantly higher (P = 0.005) in the LT group than in the HR one. The estimated freedom from recurrence was also significantly higher (P < 0.0001) for LT patients than for HR ones. Indeed, the probability of HCC recurrence after resection was higher than after transplantation achieving 31% and 76% for HR and 2% and 2% for LT at 3 and 5 years after surgery. Multivariate analysis confirmed that transplantation was superior to resection in terms of patient’s survival and risk of HCC recurrence. We conclude that LT is superior to HR for small HCC in cirrhotic patients assuming that LT should be performed within 6–10 months after listing to reduce the dropouts for reasons of tumor progression.

STEATOSIS OF THE HEPATIC GRAFT AS A RISK FACTOR FOR POST-TRANSPLANT BILIARY COMPLICATIONS

Baccarani U, Isola M, Adani GL, Avellini C, Lorenzin D, Rossetto A, Currò G, Comuzzi C, Toniutto P, Risaliti A, Soldano F, Bresadola V, De Anna D, Bresadola F. Steatosis of the hepatic graft as a risk factor for post‐transplant biliary complications.
Clin Transplant 2009 DOI: 10.1111/j.1399‐0012.2009.01128.x.
© 2009 John Wiley & Sons A/S.