Gianfranco Amicucci

Changes in the blood coagulation, fibrinolysis, and cytokine profile during laparoscopic and open cholecystectomy

Background: It has long been known that a hypercoagulability state develops after surgery. A surge in circulating cytokine levels is also commonly found in the postoperative period. These cytokines have all been shown to be capable of inducing a hypercoagulability state. Recently laparoscopic cholecystectomy (LC) has been introduced, and its advantages over the open procedure seem related to the reduced surgical trauma. LC is associated with a diminished acute-phase response compared with the open procedure. Our present knowledge on the influence of laparoscopic upon coagulation and fibrinolysis is incomplete and based on a few studies. Methods: The aim of this prospective, nonrandomized study was to investigate hemostatic system alterations in patients who undergo open and laparoscopic cholecystectomy. In addition we also measured the plasma cytokine profile to explore any relationship between changes in plasma cytokine levels and postoperative coagulation profile. Between September 1999 and April 2002, 71 patients were nonrandomly assigned to open (group 1) or laparoscopic cholecystectomy (group 2). All patients from group 1 were operated by a surgical team different from ours, who prefers the OC procedure. The patients with acute cholecystitis were excluded. Prothrombin fragment 1.2 (F1.2), thrombin-antithrombin (TAT), fibrinogen, soluble fibrin, antithrombin III (AT), protein C, plasminogen, and D-dimer levels were measured at baseline and at 1, 24, 48, and 72 h postoperatively. Serial serum levels of IL-1β and IL-6 were measured by colorimetric enzyme-linked immunosorbent assay (ELISA). Results: Plasma levels of F1.2, TAT, fibrinogen, soluble fibrin, and D-dimer increased significantly in group 1. Plasma levels of AT, protein C, and plasminogen decreased in both groups. In the OC group, the serum IL-3 and IL-6 levels began to significantly increased as early as 1 h from the beginning of the operation, revealing a peak at the sixth hour. When IL-6 and IL-1 levels were markedly elevated also, F1.2, fibrinogen, and soluble fibrin levels were increased. Conclusions: Only mild hypercoagulability was observed in patients who had undergone laparoscopic cholecystectomy. The cytokine surge was correlated with hypercoagulability. There was in fact a positive correlation between IL-6 level and hypercoagulability. The correlation between cytokine levels and coagulation activation may be related to the type of surgery performed. Further studies are required to investigate these issues.

Intestinal permeability and systemic endotoxemia after laparotomic or laparoscopic cholecystectomy.

Objective:Because laparoscopic cholecystectomy (LC) is widely recognized as a “mild” or “mini-invasive” kind of surgery, in this prospective nonrandomized study, we investigated the effect of intestinal manipulation on intestinal permeability and endotoxemia, in patients undergoing elective cholecystectomy by comparing the laparoscopic with the laparotomic approach. Summary Background Data:The intestine is susceptible to operations at remote locations, and the barrier function is altered during intestinal manipulation, leading to bacterial or endotoxin translocation into the systemic circulation. Methods:Forty-three patients undergoing elective cholecystectomy were divided into either the laparotomic (n = 22) or laparoscopic (n = 21) approach. Intestinal permeability was measured preoperatively and at day 1 and day 3 after surgery using the lactulose/mannitol absorption test. Serial venous blood samples were taken at 0, 30, 60, 90, 120, and 180 minutes, and at 12, 24, and 48 hours after surgery, for endotoxin measurement using the chromogenic limulus amoebocyte lysate assay. Results:Intestinal permeability was significantly increased at day 1 [0.106 ± 0.005 (mean ± SEM)] in the laparotomic group compared with the preoperative level (0.019 ± 0.005, P < 0.05) and to the laparoscopic group at day 1 (0.019 ± 0.005, P < 0.05), which showed no change in comparison with the preoperative level. A significantly higher concentration of systemic endotoxin was detected intraoperatively in the laparotomic group of patients in comparison to the laparoscopic group (P < 0.05). There was a significant positive correlation between systemic endotoxemia and intestinal permeability (rs = 0.958; P = 0.001). Conclusions:An increase in intestinal permeability and a greater degree of systemic endotoxemia are observed during laparotomic cholecystectomy. This suggests that intestinal manipulation may impair gut mucosal barrier function and contribute to the systemic inflammatory response see in open cholecystectomy.

Evaluation of the Maruyama Computer Program Accuracy for Preoperative Estimation of Lymph Node Metastases from Gastric Cancer

Controversy still exists about the optimal lymph node (LN) dissection for potentially curable gastric cancer. For rational LN dissection it is important to know the incidence of metastasis at each LN station. For this purpose a computer program was developed using data from 4302 primary gastric cancers treated at the National Cancer Center Hospital in Tokyo between 1969 and 1989. To evaluate the accuracy of the computer program, the differences between the individual reports generated by the computer and the stored data were investigated in 282 Italian patients submitted to curative gastrectomy and D2 or more extended LN dissections for gastric cancer. Receiver operating characteristic (ROC) analysis was used to assess the sensitivity and specificity of the program for predicting LN metastases in each of the 16 regional LN stations. The computer program showed good predictive ability for LN metastases in most of the 16 LN stations, as the areas under the curve ranged from 0.741 (station 15) to 0.944 (station 8), with a mean of 0.856. A critical cutoff point of 18% of the programs expected percentage was the value maximizing the validity of the prediction. Using an “absolute” cutoff point of 0%, the overall rate of false-negative (FN) predictions in 176 N+ patients was 11.9%; of these, 11 (6.2%) were absolute FNs, in which the program totally failed to estimate LN metastases; the remaining 10 cases (5.7%) were relative FNs because the specific prediction was positive for a different depth of stomach invasion. The low number of D3/D4 lymphadenectomies in the historical database may affect the low estimate of metastases to N3/N4 nodes generated by the program. Based on these data, the program predicts with good accuracy the extent of LN metastases from gastric cancer, but it is not recommended for directing the surgeon to perform more extensive lymphadenectomy.

Dexamethasone for the Prevention of Recurrent Laryngeal Nerve Palsy and Other Complications After Thyroid Surgery A Randomized Double-Blind Placebo-Controlled Trial

IMPORTANCE Recurrent laryngeal nerve dysfunction and hypoparathyroidism are well-recognized, important complications of thyroid surgery. The duration of convalescence after noncomplicated thyroid operation may depend on several factors, of which pain and fatigue are the most important. Nausea and vomiting occur mainly on the day of operation. Glucocorticoids are well known for their analgesic, anti-inflammatory, immune-modulating and antiemetic effects. However, there is little information in the literature on the use of steroids in thyroid surgery, and the information that is available is conflicting. OBJECTIVE To investigate whether preoperative dexamethasone could improve surgical outcome in patients undergoing thyroid surgery. DESIGN A randomized double-blind placebo-controlled trial. A 30-day follow-up for morbidity was performed in all cases. SETTING All patients were hospitalized in a public hospital. PARTICIPANTS From June 2008 through August 2011, 328 patients were randomized to receive either intravenous dexamethasone, 8 mg, administered 90 minutes before skin incision, or saline solution (placebo). INTERVENTIONS Intravenous dexamethasone, 8 mg. MAIN OUTCOMES AND MEASURES The primary end points were temporary or permanent recurrent laryngeal nerve palsy. Transient and definitive hypoparathyroidism, pain and fatigue scores, nausea, and the number of vomiting episodes were also registered. Preoperatively and at several times during the first 24 postoperative hours, we measured C-reactive protein, interleukin 6, and interleukin 1β levels. RESULTS In the dexamethasone group, the rate of temporary recurrent laryngeal nerve palsy (4.9%) was significantly lower compared with the placebo group (8.4%) (P = .04). Also, postoperative transient biochemical hypoparathyroidism occurred more frequently in the placebo group (37.0%) than in the dexamethasone group (12.8%). Dexamethasone use significantly reduced postoperative levels of C-reactive protein (P = .01) and interleukin 6 and interleukin 1β (P = .02), fatigue (P = .01), and overall pain during the first 24 postoperative hours (P = .04), as well as the total analgesic (ketorolac tromethamine) requirement (P = .04). Dexamethasone use also reduced nausea and vomiting on the day of operation (P = .045). CONCLUSIONS AND RELEVANCE Preoperative administration of dexamethasone, 8 mg, reduced postoperative temporary recurrent laryngeal nerve palsy and hypoparathyroidism rates and reduced pain, fatigue, nausea, and vomiting after thyroid surgery. However, these data require further analysis in randomized prospective studies. TRIAL REGISTRATION clinicaltrials.gov Identifier:NCT01690806.

Systemic inflammation and immune response after laparotomy vs laparoscopy in patients with acute cholecystitis, complicated by peritonitis

AIM To evaluate acute cholecystitis, complicated by peritonitis, acute phase response and immunological status in patients treated by laparoscopic or open approach. METHODS From January 2002 to May 2012, we conducted a prospective randomized study on 45 consecutive patients (27 women, 18 men; mean age 58 years). These subjects were taken from a total of 681 patients who were hospitalised presenting similar preoperative findings: acute upper abdominal pain with tenderness, involuntary guarding under the right hypochondrium and/or in the flank; fever higher than 38 °C, leukocytosis greater than 10 × 10(9)/L or both, and ultrasonographic evidence of calculous cholecystitis possibly complicated by peritonitis. These patients had undergone cholecystectomy for acute calculous cholecystitis, complicated by bile peritonitis. Randomly, 23 patients were assigned to laparoscopic cholecystectomy (LC), and 22 patients to open cholecystectomy (OC). Blood samples were collected from all patients before operation and at days 1, 3 and 6 after surgery. Serum bacteraemia, endotoxaemia, white blood cells (WBCs), WBC subpopulations, human leukocyte antigen-DR (HLA-DR), neutrophil elastase, interleukin-1 (IL-1) and IL-6, and C-reactive protein (CRP) were measured at 0, 30, 60, 90, 120 and 180 min, at 4, 6, 12, 24 h, and then daily (8 A.M.) until post-op day 6. RESULTS The two groups were comparable in the severity of peritoneal contamination as indicated by the viable bacterial count (open group = 90% of positive cultures vs laparoscopic group = 87%) and endotoxin level (open group = 33.21 ± 6.32 pg/mL vs laparoscopic group = 35.02 ± 7.23 pg/mL). Four subjects in the OC group (18.1%) and 1 subject (4.3%) in the LC group (P < 0.05) developed intra-abdominal abscess. Severe leukocytosis (range 15.8-19.6/mL) was observed only after OC but not after LC, mostly due to an increase in neutrophils (days 1 and 3, P < 0.05). This value returned to the normal range within 3-4 d after LC and 5-7 d after OC. Other WBC types and lymphocyte subpopulations showed no significant variation. On the first day after surgery, a statistically significant difference was observed in HLA-DR expression between LC (13.0 ± 5.2) and OC (6.0 ± 4.2) (P < 0.05). A statistically significant change in plasma elastase concentration was recorded post-operatively at days 1, 3, and 6 in patients from the OC group when compared to the LC group (P < 0.05). In the OC group, the serum levels of IL-1 and IL-6 began to increase considerably from the first to the sixth hour after surgery. In the LC group, the increase of serum IL-1 and IL-6 levels was delayed and the peak values were notably lower than those in the OC group. Significant differences between the groups, for these two cytokines, were observed from the second to the twenty-fourth hour (P < 0.05) after surgery. The mean values of serum CRP in the LC group on post-operative days (1 and 3) were also lower than those in the OC group (P < 0.05). Systemic concentration of endotoxin was higher in the OC group at all intra-operative sampling times, but reached significance only when the gallbladder was removed (OC group = 36.81 ± 6.4 ρg/mL vs LC group = 16.74 ± 4.1 ρg/mL, P < 0.05). One hour after surgery, microbiological analysis of blood cultures detected 7 different bacterial species after laparotomy, and 4 species after laparoscopy (P < 0.05). CONCLUSION OC increased the incidence of bacteraemia, endotoxaemia and systemic inflammation compared with LC and caused lower transient immunological defense, leading to enhanced sepsis in the patients examined.

Peritonitis from Perforated Peptic Ulcer and Immune Response

ABSTRACT This article has been retracted

Laparoscopy-assisted ventriculoperitoneal shunt surgery: personal experience and review of the literature

Ventriculoperitoneal shunting is a widely accepted technique for the treatment of hydrocephalus. The standard procedure to insert the peritoneal catheter requires an abdominal incision, muscle dissection, and opening of the peritoneum. A number of complications related to the abdominal surgical phase have been reported. Laparoscopy-assisted ventriculoperitoneal shunting is a valid alternative procedure that reduces surgical trauma. We describe our experience and review the literature. A total of 30 laparoscopically guided ventriculoperitoneal shunting procedures were performed between January 2007 and June 2008, in collaboration with a general surgeon experienced in laparoscopy. Of these procedures, 25 were new shunt placements and 5 were revisions. Data about operative time, outcome, and complications were registered and compared with a group of 30 patients treated by means of standard laparotomy in the period 2005–2007. Laparoscopic shunt placement was successful in all patients. Operative duration, complications, and postoperative pain were all lower in patients treated by laparoscopy as compared to the laparotomy. In the laparoscopic group, an earlier peristalsis, quicker mobilization, and better cosmetic results were also noted. Laparoscopy in both ventriculoperitoneal shunt placement and revision is a safe, effective, and minimally invasive technique. It ensures proper abdominal placement of the distal catheter under direct vision allowing confirmation of its patency.

Deliberate hypoxic pelvic and limb chemoperfusion in the treatment of recurrent melanoma

BACKGROUND The treatment of patients with advanced or recurrent pelvic melanoma, which are often associated with lesions in the lower limbs, is still unsatisfactory and controversial. A simplified hypoxic pelvic and limb perfusion has been recently recommended to provide therapeutic options for palliation and possibly cure. METHODS A nonrandomized and noncontrolled phase II experimental study was performed in 11 patients with symptomatic unresectable recurrent melanoma of the pelvis and limb. Patients were submitted to hypoxic pelvic and limb perfusion with 25 mg/m(2) of melphalan, 50 mg/m(2) of cisplatin, 300 mg/m(2) of dacarbazine, and 75 mg/m(2) of epirubicin by means of a simplified balloon occlusion technique. Response rate and time to disease progression were the primary endpoints; overall survival was the secondary endpoint. RESULTS During the procedures there were no technical, hemodynamic, or vascular complications, and no deaths occurred during surgery or in the postoperative period. Response rate was 82% (95% confidence interval, 58% to 100%). Median time to disease progression was 12 months (range 9 to 30 months). Three-year overall survival was 34%. CONCLUSIONS Hypoxic pelvic and limb perfusion is a safe and good palliative treatment for patients with unresectable recurrent melanoma. Further studies are necessary to to confirm these data and to establish if refinements can be made with acceptable toxicity.

New ultrasonic dissector versus conventional hemostasis in thyroid surgery: a randomized prospective study.

BACKGROUND The ultrasonic dissector (UD) is an instrument that uses vibration to coagulate and cut tissue simultaneously. The main advantage of a UD instrument compared with a standard electrosurgical device is represented by minimal lateral thermic tissue damage allowing a wide application in thyroid surgery. A new UD (NUD), with a tip smaller than 5 mm, might enable a more precise dissection near vital structures such as parathyroid glands and recurrent laryngeal nerve. To evaluate the NUD during thyroid surgery, a prospective randomized study was performed using the new device versus traditional procedures. SUBJECTS AND METHODS Two hundred sixty-one patients underwent various thyroid surgical procedures; they were randomly assigned (130 in the NUD group and 131 in the conventional hemostasis [CH] group). The two surgical groups were compared in age, sex, diagnosis, thyroid size, operative time, drainage volume during the first 24-48 hours after surgery, and complications (hypoparathyroidism, damage of the recurrent laryngeal nerve, and postoperative pain). RESULTS The two groups were similar regarding age, sex, numbers of lobectomies and total thyroidectomies, and numbers of focal and diffuse pathologies. Mean ± standard deviation operative time was shorter in the NUD group compared with the CH group for both lobectomy (70 ± 21 minutes versus 99 ± 27 minutes; P<.01) and total thyroidectomy (91 ± 37 minutes versus 121 ± 42 minutes; P=.01) procedures. No difference was found regarding the amount of drainage volume for different procedures (P=not significant). Postoperative transient (P=.01) and definitive (P=.01) hypoparathyroidism occurred more frequently in the CH group than in the NUD group. There was a significant difference regarding the transient damage of the recurrent laryngeal nerve: 7 patients (5.3%) in the NUD group and 13 patients (9.8%) in the CH group (P=.01). There was no difference regarding definitive damage to the recurrent laryngeal nerve and pain. CONCLUSION This NUD may reduce the rate of complications (transient and definitive hypocalcemia, transient damage of the recurrent laryngeal nerve) and operative time.

Laparoscopic versus open appendectomy in obese patients: A meta-analysis of prospective and retrospective studies

BACKGROUND: A meta-analysis of different kinds of studies was performed to assess outcomes of laparoscopic versus open appendectomy in obese patients. MATERIALS AND METHODS: Retrospective and prospective studies enrolling patients with a body mass index greater than 30 kg/m2 were included. Primary outcomes were days of hospital stay, surgical procedure duration, and overall post-operative complication rate. Secondary outcomes were wound infection and intra-abdominal abscesses formation rate, hospital charges. RESULTS: Laparoscopic appendectomy showed to be significantly associated with lower wound infection (P < 0.001) and post-operative complication rate (P < 0.001). Surgical time was considered as a hallmark of technical challenge and resulted diminished in the laparoscopic group (P = 0.018). Although not clinically relevant per se, the statistically significant shorter hospital stay (P < 0.001) was probably the reason of decreased hospital charges (P < 0.001). Intra-abdominal abscesses formation rate was higher in the open appendectomy group (P = 0.058), although slightly above the statistical significance threshold. CONCLUSION: Laparoscopic approach seemed to show relevant advantages compared to open appendectomy, but a large prospective trial is necessary to collect high quality data and investigate long-term outcomes.