Impact of laparoscopy on oncological outcomes after colectomy for stage III colon cancer: A post-hoc multivariate analysis from PETACC8 European randomized clinical trial.

BACKGROUND: In colon cancer (CC), surgery remains the mainstay of treatment with curative intent. Despite several clinical trials comparing open and laparoscopic approaches, data on long-term outcomes for stage III CC are lacking. METHODS: This post-hoc analysis of the European PETACC8 randomized phase 3 trial included patients from 340 sites between December 2005 and November 2009, with long follow-up (median 7.56 years). Patients were randomly assigned to FOLFOX or FOLFOX+cetuximab after colonic resection. The surgical approach was left to the referring surgeon's discretion. RESULTS: Among 2555 patients included, 1796 (70.29%) were operated on by open surgery and 759 (29.71%) by laparoscopy. The 5-year OS rate was better after laparoscopic resection (85.4%, 95%CI 82.5-87.7) than after open surgery (80.2%, 95%CI 78.2-82.0; p = 0.002). The 5-year DFS rate was also better after laparoscopy (p = 0.016). However, in multivariate analysis using a propensity matching, the surgical approach was not found to be an independent prognostic factor for OS or DFS. OS (p = 0.0243) and DFS (p = 0.035) were increased after laparoscopic surgery in KRAS/BRAF WT sub-group CONCLUSION: We showed that laparoscopic resection has comparable long-term outcomes to open surgery in patients with stage III CC. For those with RAS and BRAF WT CC, laparoscopic colectomy may favorably impact survival.

Practical impact of a decision support for goal-directed fluid therapy on protocol adherence: a clinical implementation study in patients undergoing major abdominal surgery.

The purpose of this study was to assess the effects of using a real time clinical decision-support system, "Assisted Fluid Management" (AFM), to guide goal-directed fluid therapy (GDFT) during major abdominal surgery. We compared a group of patients managed using the AFM system with a historical cohort of patients (control group) who had been managed using a manual GDFT strategy. Adherence to the protocol was defined as the relative intraoperative time spent with a stroke volume variation (SVV) < 13%. We hypothesised that patients in the AFM group would have more time during surgery with a SVV < 13% compared to the control group. All patients had a radial arterial line connected to a pulse contour analysis monitor and received a 2 ml/kg/h maintenance crystalloid infusion. Additional 250 ml crystalloid boluses were administered whenever measured SVV ≥ 13% in the control group, and when the software suggested a fluid bolus in the AFM group. We compared 46 AFM-guided patients to 38 controls. Patients in the AFM group spent significantly more time during surgery with a SVV < 13% compared to the control group (median 92% [82, 96] vs. 76% [54, 86]; P < 0.0005), and received less fluid overall (1775 ml [1225, 2425] vs. 2350 ml [1825, 3250]; P = 0.010). The incidence of postoperative complications was comparable in the two groups. Implementation of a decision support system for GDFT guidance resulted in a significantly longer period during surgery with a SVV < 13% with a reduced total amount of fluid administered. Trial registration: Clinical Trials.gov (NCT03141411).

Expansion of memory-type CD8+ T cells correlates with the failure of early immunosuppression withdrawal after cadaver liver transplantation using high-dose ATG induction and rapamycin.

BACKGROUND: We report on a pilot study investigating the feasibility of early immunosuppression withdrawal after liver transplantation (LT) using antithymocyte globulin (ATG) induction and rapamycin. METHODS: LT recipients received 3.75 mg/kg per day ATG from days 0 to 5 followed by rapamycin-based immunosuppression. In the absence of acute rejection (AR), rapamycin was withdrawn after month 4. Immunomonitoring included analysis of peripheral T-cell phenotypes and clonality, cytokine production in mixed lymphocyte reaction, and characterization of intragraft infiltrating cells. RESULTS: Ten patients were enrolled between October 2009 and July 2010. In the first three patients, complete withdrawal of immunosuppression after month 4 led to AR. No further withdrawals of immunosuppressive were attempted. Two AR occurred in the remaining seven patients. ATG induced profound T-cell depletion followed by CD8(+) T-cell reexpansion exhibiting memory/effector-like phenotype associated with progressive oligoclonal T-cell expansion (Vß/HPRT ratio) and gradually enhanced anti-cytomegalovirus and anti-Epstein-Barr virus T-cell frequencies. Patients developing AR were characterized by decreased TCAIM expression. AR were associated with increased donor-specific production of interferon (IFN)-γ and interleukin (IL)-17, increased intragraft expression of IFN-γ mRNA, and significant CD8(+) T-cell infiltrates colocalizing with IL-17(+) cells. CONCLUSION: High-dose ATG followed by short-term rapamycin treatment failed to promote early operational tolerance to LT. AR correlates with expansion of memory-type CD8(+) T cells and increased levels of IFN-γ and IL-17 in mixed lymphocyte reaction and in the graft. This suggests that resistance and preferential expansion of effector memory T-cell in lymphopenic environment could represent the major barrier for establishment of tolerance to LT in approaches using T-cell-depleting induction.

Acute liver transplant rejection upon immunosuppression withdrawal in a tolerance induction trial: potential role of IFN-gamma-secreting CD8+ T cells.

We designed a pilot trial in cadaveric liver transplantation to determine whether induction with antithymocyte globulins (ATG) and sirolimus would allow immunosuppression withdrawal. Patients received ATG 3.75 mg/kg per day from day 1 to 5 after transplantation followed by sirolimus for 4 to 6 months. We monitored interleukin (IL)-7 serum levels, interferon (IFN)-gamma, and IL-2 mRNA accumulation in mixed leukocyte reaction and intragraft IFN-gamma mRNA expression. In the first three patients, immunosuppression discontinuation was followed by reversible acute rejection occurring on days 280, 246, and 163 posttransplantation, corresponding to days 140, 40, and 39 after drug withdrawal, respectively. At the time of rejection, blood CD8+ T-cells counts had returned to or above pretransplant levels in two of three patients, whereas CD4+ T-cell count remained low. IL-7 serum levels rose in all three patients in the first months after transplantation and IFN-gamma mRNA accumulated in mixed leukocyte reaction between recipient T cells and donor spleen cells at the time of rejection. High levels of IFN-gamma mRNA were consistently detected in liver biopsy performed at the time of rejection. In conclusion, lymphopenia-induced IL-7 production after induction with ATG and sirolimus might lead to emergence of IFN-gamma-secreting CD8+ T-cells responsible for acute rejection after immunosuppression withdrawal.

Induction chemotherapy does not increase the operative risk of pneumonectomy!

BACKGROUND: There is an ongoing debate whether induction therapy increases post-operative mortality and morbidity, especially when performing pneumonectomy. We therefore reviewed a consecutive series of patients having undergone pneumonectomy in a single center. METHODS: The charts of 298 patients operated on between January 1999 and July 2005 were reviewed. Patients were divided into two groups: group 1 included those who received induction chemotherapy (60 patients, 20.1%), and group 2 included those who underwent surgery alone (238 patients, 79.9%). Endpoints were operative mortality at 30 and at 90 days, and major complications such as empyema, bronchial fistula and acute respiratory distress syndrome. Statistical analyses were performed using SPSS 11.0 software. RESULTS: Demographic data were similar for both groups when considering side of operation, comorbidity and weaning from tobacco; patients were older in group 2 (61.83+/-9.58 years vs 57.75+/-8.94 years; p=0.003) and there were more female patients in group 2 (17.2% vs 5.0%; p=0.010). Post-operative mortality at 30 days was 6.7% in group 1 and 5.5% in group 2 (p=0.458), and 11.7% for group 1 and 10.9% in group 2 at 90 days (p=0.512). Incidence of empyema was 1.7% in group 1 and 2.1% in group 2 (p=0.652); incidence of bronchopleural fistulas was 1.7% in group 1 and 5.5% in group 2 (p=0.188); incidence of acute respiratory distress syndrome was 3.3% in group 1 and 3.4% in group 2 (p=0.675). CONCLUSION: In opposition to previous reports, induction chemotherapy did not significantly jeopardize post-operative outcome following pneumonectomy in our experience.

Surgical treatment of ankle fractures by pneumatic stapling: clinical experience and review of the literature.

Between June 1987 and December 2002, 237 cases of malleolar fractures were treated at Erasme Hospital using pneumatic stapling, alone or combined with another type of fixation. This retrospective study addresses 176 well-documented cases. The mean follow-up period was 36 months. The results indicate that pneumatic stapling is an effective technique with a very low rate of failure. Comminuted fractures are not a contraindication.

Pediatric en bloc dual kidney-pancreas transplantation into an adult recipient: a simplified technique. Benefits of the en bloc kidney-pancreas transplantation technique in pediatric donors.

The lower age limit for pancreas donors is not well defined. Fear of inadequate islet beta-cell mass and of technical complications has hampered the use of pediatric donors. A surgical technique of 'en bloc' kidney-pancreas is described. Both kidneys and pancreas were removed en bloc from a 13-kg, 31-month-old child. During bench preparation, one anastomosis was performed between the portal vein and the inferior vena cava. The proximal end of the aorta was closed. The bloc was transplanted into a 36-year-old type I diabetic patient intraperitoneally in the right iliac fossa. The kidneys functioned immediately. Pancreatic graft function resumed after POD 15 but insulin therapy was maintained until POD 112. Currently, the patient retains excellent kidney and pancreas graft functions. Very young donors can be accepted as pancreas donors for adult recipients, although slow recovery of pancreatic function can be expected. Use of the en bloc technique is well suited for very small children, as it prevents potential vascular complications.