Ilker Iskender

Is there any maximum standardized uptake value variation among positron emission tomography scanners for mediastinal staging in non-small cell lung cancer?

The maximum standardized uptake value (SUV(max)) varies among positron emission tomography-integrated computed tomography (PET/CT) centers in the staging of non-small cell lung cancer. We evaluated the ratio of the optimum SUV(max) cut-off for the lymph nodes to the median SUV(max) of the primary tumor (ratioSUV(max)) to determine SUV(max) variations between PET/CT scanners. The previously described PET predictive ratio (PPR) was also evaluated. PET/CT and mediastinoscopy and/or thoracotomy were performed on 337 consecutive patients between September 2005 and March 2009. Thirty-six patients were excluded from the study. The pathological results were correlated with the PET/CT findings. Histopathological examination was performed on 1136 N2 lymph nodes using 10 different PET/CT centers. The majority of patients (group A: 240) used the same PET/CT scanner at four different centers. Others patients were categorized as group B. The ratioSUV(max) for groups A and B was 0.18 and 0.22, respectively. The same ratio for centers 1, 2, 3 and 4 was 0.2, 0.21, 0.21, and 0.23, respectively. The optimal cut-off value of the PPR to predict mediastinal lymph node pathology for malignancy was 0.49 (likelihood ratio +2.02; sensitivity 70%, specificity 65%). We conclude that the ratioSUV(max) was similar for different scanners. Thus, SUV(max) is a valuable cut-off for comparing-centers.

False-positivity of mediastinal lymph nodes has negative effect on survival in potentially resectable non-small cell lung cancer†

OBJECTIVESnIt has been shown that increased metabolic activity of primary tumour has a negative effect on survival in non-small cell lung cancer (NSCLC) staged with positron emission tomography integrated computed tomography (PET/CT). We hypothesized that an increased metabolic activity of mediastinal lymph nodes would have worse survival even if it is false.nnnMETHODSnThree hundred and twenty-eight consecutive patients with NSCLC histology were imaged with PET/CT within 90 days of surgery between September 2005 and March 2009. Patients who had neoadjuvant chemotherapy (n = 22), patients with prior history of NSCLC (n = 9) or other malignancies within 5 years (n = 11) were excluded from the study. Patients with negative mediastinoscopy underwent resection. Pathological results were revised according to the seventh tumor-node-metastasis staging system. Kaplan-Meier test was used for survival. Log-rank and Cox analyses were used for comparisons.nnnRESULTSnA total of 286 patients (262 male; mean age: 58.5 years) were evaluated. There were 22 (6.7%) operative deaths and none of the patients were lost to follow-up. The median follow-up in the remaining 264 patients was 26 months (range, 2-61 months). Tumour size, nodal spread and stage were all strongly associated with survival from NSCLC (P < 0.001). There were 63 true-positive, 65 false-positive (FP), 152 true-negative (TN) and six false-negative findings on mediastinal staging after PET/CT. The maximum standardized uptake value of primary tumour was significantly higher in FP patients than in TN patients (P = 0.012). After excluding pN2-positive patients, TN patients had better survival than FP patients (P = 0.006). Multivariate analysis showed that false-positivity of mediastinal lymph nodes was independently associated with worse survival (hazard ratio = 0.63; P = 0.02). There were 146 patients with pT1-4, pN0 treated with R0 surgical resection. Disease-free survival and overall survival were also significantly better for TN patients in completely resected group (P = 0.009 versus 0.016).nnnCONCLUSIONSnWe have shown that false-positivity of mediastinal lymph nodes had yielded worse survival in surgically staged or resected NSCLC patients staged with PET/CT. This result may help to allocate patients with potentially poor prognosis for considered additional therapy.

Cytokine filtration modulates pulmonary metabolism and edema formation during ex vivo lung perfusion

BACKGROUNDnEx vivo lung perfusion (EVLP) has improved the process of donor lung management. Cytokine accumulation during EVLP has been shown to correlate with worse outcome after lung transplantation. Our objective in this study was to test the safety and efficacy of cytokine filtration during EVLP in a large animal model.nnnMETHODSnPig donor lungs were preserved for 24 hours at 4°C, followed by 12 hours of EVLP, according to the Toronto protocol. The perfusate was continuously run through an absorbent device (CytoSorb) via a veno-venous shunt from the reservoir in the filter group. EVLP was performed according to the standard protocol in the control group (n = 5 each). EVLP physiology, lung X-ray, perfusate biochemistry, inflammatory response and microscopic injury were assessed.nnnRESULTSnCytokine filtration significantly improved airway pressure and dynamic compliance during the 12-hour perfusion period. Lung X-rays acquired at the end of perfusion showed increased consolidation in the control group. Electrolyte imbalance, determined by increased hydrogen, potassium and calcium ion concentrations in the perfusate, was markedly worsened in the control group. Glucose consumption and lactate production were markedly reduced, along with the lactate/pyruvate ratio in the filter group. Cytokine expression profile, tissue myeloperoxidase activity and microscopic lung injury were significantly reduced in the filter group.nnnCONCLUSIONSnContinuous perfusate filtration through sorbent beads is effective and safe during prolonged EVLP. Cytokine removal decreased the development of pulmonary edema and electrolyte imbalance through the suppression of anaerobic glycolysis and neutrophil activation in this setting. Further studies are needed to test the beneficial effect of cytokine filtration on post-transplant lung function.

Ex vivo treatment with inhaled N-acetylcysteine in porcine lung transplantation

BACKGROUNDnWe have shown the beneficial effects of N-acetylcysteine (NAC) on posttransplant lung function, when both donor and recipient were pretreated intravenously. However, systemic treatment of multiorgan donors may not be clinically relevant. Thus, we hypothesized that exxa0vivo treatment of donors with nebulized NAC would be adequate to prevent from ischemia-reperfusion injury after lung transplantation.nnnMETHODSnLungs were retrieved from domestic pigs and stored at 4°C for 24 h followed by 2 h of exxa0vivo lung perfusion (EVLP) to administer 50xa0mg/kg of NAC via nebulization in the NAC group (nxa0=xa06). The control group received nebulized saline (nxa0=xa05). Left lungs were transplanted and isolated at 1 h of reperfusion by occluding the right main bronchus and pulmonary artery, followed by 5 h of observation. Physiological data during EVLP and after reperfusion were recorded. Inflammatory response, markers of oxidative stress, and microscopic lung injury were analyzed.nnnRESULTSnThere was a trend toward better oxygenation throughout reperfusion period in the treatment group, which was accompanied by inhibited inflammatory response related to reduction in myeloperoxidase activity during EVLP and nuclear factor-κB activation at the end of reperfusion.nnnCONCLUSIONSnExxa0vivo treatment of donor lungs with inhaled NAC reduced inflammatory response via its antioxidant activity in experimental porcine lung transplantation.

Ex vivo administration of trimetazidine improves post-transplant lung function in pig model

OBJECTIVESnEx vivo lung perfusion (EVLP) is not only used to assess marginal donor lungs but is also used as a platform to deliver therapeutic agents outside the body. We previously showed the beneficial effects of trimetazidine (TMZ) on ischaemia reperfusion (IR) injury in a rat model. This study evaluated the effects of TMZ in a pig EVLP transplant model.nnnMETHODSnPig lungs were retrieved and stored for 24u2009h at 4°C, followed by 4u2009h of EVLP. Allografts were randomly allocated to 2 groups ( n u2009=u20095 each). TMZ (5u2009mg/kg) was added to the prime solution prior to EVLP. After EVLP, left lungs were transplanted and recipients were observed for 4u2009h. Allograft gas exchange function and lung mechanics were recorded hourly throughout reperfusion. Microscopic lung injury and inflammatory and biochemical parameters were assessed.nnnRESULTSnThere was a trend towards better oxygenation during EVLP in the TMZ group ( P u2009=u20090.06). After transplantation, pulmonary gas exchange was significantly better during the 4-h reperfusion period and after isolation of the allografts for 10u2009min ( P u2009<u20090.05). Tissue thiobarbituric acid levels, myeloperoxidase activity and protein concentrations in bronchoalveolar lavage samples were significantly lower in the TMZ group at the end of EVLP ( P u2009<u20090.05).nnnCONCLUSIONSnEx vivo treatment of donor lungs with TMZ significantly improved immediate post-transplant lung function. Further studies are warranted to understand the effect of this strategy on long-term lung function.

Previous lung volume reduction surgery does not negatively affect survival after lung transplantation

OBJECTIVESnLung volume reduction surgery (LVRS) and lung transplantation (LTx) are the treatments of choice in selected patients with end-stage emphysema. Recently, the history of LVRS has been questioned due to reduced post-transplant survival. We aim to address this question by reviewing our experience, which is the largest single-centre series of LVRS followed by LTx.nnnMETHODSnWe reviewed our prospectively recorded database in patients with emphysema undergoing LTx between 1993 and 2014. Preoperative workup and postoperative outcomes were compared according to previous LVRS status. The Kaplan-Meier test was used for survival analysis and compared with a log-rank test.nnnRESULTSnOne hundred and seventeen patients (66 men; mean age 56u2009±u20097u2009years) underwent LTx during the study period, 52 of whom had previous LVRS (LVRSu2009+u2009LTx). The mean time from LVRS to LTx was 45u2009±u200931u2009months. Patients were slightly older and had extensive smoking history in the LVRSu2009+u2009LTx group. Overall, in-hospital mortality was 10%, which did not differ significantly regardless of the history of LVRS (Pu2009=u20090.8). The median survival for the LTx-only and LVRSu2009+u2009LTx groups was 86 [95% confidence interval (CI) 56-116] and 107 (95% CI 77-137)u2009months, respectively (Pu2009=u20090.6).nnnCONCLUSIONSnPrevious LVRS does not negatively affect short-term and long-term outcomes following LTx in patients with end-stage emphysema. The history of LVRS should not preclude the candidacy for LTx. Considering the limited number of donors available, the LVRS option should be kept in mind for the postponement of LTx in carefully selected patients.

Anaesthesiology and intensive care Comparison of continuous use of thoracic epidural analgesia and intercostal block for pain management after thoracotomy

Aim of the study: We aimed to compare the efficacy of the continuous use of thoracic epidural and intercostal analgesia for post-thoracotomy pain. Material and methods: Sixty patients completed a prospective, randomized, double-blinded study. The patients were randomized to receive thoracic epidural (group 1, n = 30) or intercostal block (group 2, n = 30) for 24 hours. In both groups, 0.25% bupivacaine was infused at a rate of 5 ml/h through an inserted catheter. Visual analog scale at rest (VAS-R) and after coughing (VAS-C) scores were recorded at baseline and at 1, 6 and 24 hours after surgery to evaluate pain. Morphine consumption, complications and side effects were recorded as well. Results: VAS-R and VAS-C scores were similar at baseline; however, 1 st , 6 th and 24 th hour scores of group 1 were signifi cantly lower than the scores of group 2 (for VAS-R; p = 0.017, p = 0.001, p = 0.023, for VAS-C; p = 0.006, p = 0.002, p = 0.032, respectively). 24-hour morphine consumption was lower in group 1 in comparison to group 2 (p = 0.032). In group 1, 5 out of 30 patients (17%) experienced hypotension, compared with none in group 2 (p = 0.02). Conclusions: For post-thoracotomy pain, better control of analgesia is observed with the thoracic epidural technique; however, intercostal block constitutes an alternative method as it is characterized by lower incidence of hypotension.

The Experimental Use of N-Butyl Cyanoacrylate Tissue Adhesive in Pulmonary Wedge Resections

BACKGROUNDnIn this experimental study, the effectiveness of N-butyl cyanoacrylate tissue adhesive on preventing air leakage after pulmonary wedge resection was observed.nnnMETHODSnTwenty pairs of sheep lungs were used. Before initiating the study, the sheep lungs were ventilated to identify any air leakage from the parenchyma. On positive results, those sheep lungs were then excluded from the study. Wedge resection was performed on the right and left lower lobes of sheep lungs by clamping the edges forming a triangle of 5 cm × 5 cm × 5 cm. One side of parenchyma was sutured by 3/0 vicryl (Group A) while the other side of parenchyma was sealed by N-butyl cyanoacrylate (Group B). After waiting for 5 min for N-butyl cyanoacrylate to dry, the sheep lungs were intubated by 6F endotracheal tubes. The lungs were soaked in a bath tub filled with 10 cm deep water and inflated by 40 mmHg pressure to record any air leakage from the parenchyma partially sutured by vicryl and sealed by N-butyl cyanoacrylate.nnnRESULTSnAir leakages were observed on the parenchyma surfaces of group of lungs (100%) sutured by vicryl (minimal 30%, mild 50% or massive 20% levels), while only on four of (20%) the other group of lungs sealed by N-butyl cyanoacrylate, minimal air leakage was observed on the parenchymal surface. There was an extremely significant difference between Group A and Group B in terms of the development of air leakage (p=000).nnnCONCLUSIONnWe consider that, N-butyl cyanoacrylate could be used effectively and safely to prevent air leakage from the pulmonary wedge resection surface.