Panagiotis Hountis

Low incidence of bronchopleural fistula after pneumonectomy for lung cancer.

Bronchopleural fistula (BPF) after pneumonectomy for NSCLC remains a highly morbid complication. We examined possible factors including the surgical techniques associated with BPF development. From 221 pneumonectomies for NSCLC, bronchial stump closure was mechanically performed in 192 patients and manually in the remaining 29. In all right-sided pneumonectomies mechanical closure was performed with associated stump coverage. In 114/130 left-sided procedures where mechanical closure was selected, bronchial stump remained uncovered. In the remaining 16 left-sided cases where manual stump closure was selectively performed, the stump was covered utilizing various tissues. Risk factors were classified into preoperative, intra-operative and postoperative. Five patients (2.3%) developed BPF. Univariate analysis revealed peri-operative transfusion, respiratory infection at the time of presentation, neoadjuvant therapy, right-sided pneumonectomy, manual type of bronchial closure, days of postoperative hospitalization and mechanical ventilation as significant risk factors for BPF development. Multivariate analysis followed revealing preoperative respiratory infection and right pneumonectomy as the only independent risk factors. In our series, a selected stump coverage policy showed a low incidence of BPF development. Mechanical stapling was superior to manual closure, although not as an independent factor. Early recognition of possible risk factors associated with fistula development is of paramount importance.

γ-H2AX expression detected by immunohistochemistry correlates with prognosis in early operable non-small cell lung cancer

Background Phosphorylation of the H2AX histone is an early indicator of DNA double-strand breaks and of the resulting DNA damage response. In the present study, we assessed the expression and prognostic significance of γ-H2AX in a cohort of 96 patients with operable non-small cell lung carcinoma. Methods Ninety-six paraffin-embedded specimens of non-small cell lung cancer patients were examined. All patients underwent radical thoracic surgery of primary tumor (lobectomy or pneumonectomy) and regional lymph node dissection. γ-H2AX expression was assessed by standard immunohistochemistry. Follow-up was available for all patients; mean duration of follow-up was 27.50 ± 14.07 months (range 0.2–57 months, median 24 months). Results Sixty-three patients (65.2%) died during the follow-up period. The mean survival time was 32.2 ± 1.9 months (95% confidence interval [CI]: 28.5–35.8 months; median 30.0 months); 1-, 2- and 3-year survival rates were 86.5% ± 3.5%, 57.3% ± 5.1%, and 37.1% ± 5.4%, respectively. Low γ-H2AX expression was associated with a significantly better survival as compared with those having high γ-H2AX expression (35.3 months for low γ-H2AX expression versus 23.2 months for high γ-H2AX expression, P = 0.009; hazard ratio [HR] 1.95, 95% CI: 1.15–3.30). Further investigation with multivariate Cox proportional hazards regression analysis revealed that high expression of γ-H2AX remained an independent prognostic factor of shorter overall survival (HR 2.15, 95% CI: 1.22–3.79, P = 0.026). A combined p53/γ-H2AX analysis was performed, and we found that the p53 low/γ-H2AX low phenotype was associated with significantly better survival compared with all other phenotypes. Conclusion Our study is the first to demonstrate that expression of γ-H2AX detected by immunohistochemistry may represent an independent prognostic indicator of overall survival in patients with non-small cell lung cancer. Further studies are needed to confirm our results.

H2AX a Promising Biomarker for Lung Cancer: A Review

Histones H2A variant (H2AX) phosphorylation is an early indicator of DNA double-strand breaks formation and DNA damage response. Thus, it may act as a novel biomarker to monitor genotoxic events that can drive cancer development and tumor progression. This review will focus on the possible applications of H2AX as a key regulator of DNA damage response in lung cancer and as a biomarker of: sensitivity of lung tumors to chemotherapy and radiotherapy, treatment with PARP inhibitors, bystander effect, multistep lung carcinogenesis, environmental smoking, and chemical genotoxicity, chemoprevention, prognosis, and also as therapeutic targets in lung cancers.

Sarcomatoid lung carcinomas: a case series

We report on three Caucasian Greeks 2 males and 1 female (67, 54 and 62 years old) that were operated with sarcomatoid carcinoma of the lung, an uncommon tumor that sometimes is referred as pleomorphic carcinoma (spindle and giant cell carcinomas). These tumors are encountered in the thorax far more often than true sarcomas. There are many erroneous reports of pulmonary sarcomas made before the advent of adjunctive pathologic screening, including immunohistochemical studies. Pulmonary Sarcomatoid Carcinomas represent 0.2-1% of all lung cancers in different series and they are considered that they are not significantly aggressive than ordinary lung carcinoma.

Mechanisms of oxidative stress and myocardial protection during open-heart surgery.

Cold heart protection via cardioplegia administration, limits the amount of oxygen demand. Systemic normothermia with warm cardioplegia was introduced due to the abundance of detrimental effects of hypothermia. A temperature of 32–33°C in combination with tepid blood cardioplegia of the same temperature appears to be protective enough for both; heart and brain. Reduction of nitric oxide (NO) concentration is in part responsible for myocardial injury after the cardioplegic cardiac arrest. Restoration of NO balance with exogenous NO supplementation has been shown useful to prevent inflammation and apoptosis. In this article, we discuss the “deleterious” effects of the oxidative stress of the extracorporeal circulation and the up-to-date theories of “ideal” myocardial protection.

S100A2 protein and non-small cell lung cancer. The dual role concept.

S100A2 is a member of the EF-hand motif family S100. Its role has been recently implicated in carcinogenesis and metastasis. Although its precise role in NSCLC patients is debated and conflicting results have been published, it has been associated with patient survival. S100A2 expression was downregulated in some studies while others disagree that S100A2 is strongly expressed in lung cancer. It has been recently published by Hountis et al. that there is a significant association between nuclear S100A2 positivity and better disease-free interval. Intensity of expression was the highest in the early and advanced stages, and equally distributed in the middle stages. This is indicative for a dual role of this protein in carcinogenesis. The expression of S100A2 in operable NSCLC varies widely, and this differential location and expression pattern (nuclear or cytoplasmic or both) seem to correlate with prognosis. The precise role for the movement of S100A2 protein between cytoplasm and nucleus is still unclear. We present here a literature review, and we propose the dual concept on its substantial role as a prognostic or predictive indicator in this unfavorable group of patients.

Left atrial giant thrombus infected by Escherichia Coli. Case report

BackgroundLeft atrial thrombi are mostly related to mitral valve disease. The differential diagnosis of clots and myxomas in the left atrium is mostly based on echocardiography. Infection of intracardiac thrombi is extremely rare and mostly reported in ventricular clots or aneurysms following myocardial infarction.Case presentationWe present the case of a 65 year old female with a history of mitral valve disease and chronic atrial fibrillation who suffered repeated embolic strokes and a giant infected clot in the left atrium. Although the patient underwent prompt surgery with removal of the clot and valve replacement the complication of septic emboli to the CNS led her to death. To the best of our knowledge this is the second report of an infected left atrial thrombus.ConclusionThe case is a representative example of a neglected and undertreated patient with catastrophic consequences. Anticoagulant therapy in patients with mitral valve disease and atrial fibrillation should be applied according the currently available guidelines and standards in order to avoid analogous paradigms in the future. Mitral valve substitution should be considered in patients with mitral valve disease presenting thromboembolic complications. Surgery should be considered as the treatment of choice in cases of organized left atrial thrombus and suspected tumor or infected mass.

Prognostic significance of different immunohistochemical S100A2 protein expression patterns in patients with operable nonsmall cell lung carcinoma

S100 proteins are involved in carcinogenesis, metastasis, and survival. S100A2 is a member of the S100 family, and its expression and precise role in patients with non-small cell lung carcinoma (NSCLC) has been debated. Therefore, we examined the immunohistochemical expression patterns of S100A2 in NSCLC in relation to clinicopathological parameters, important molecular biomarkers, and patient outcome. Microarray data for 74 paraffin-embedded specimens from patients with NSCLC were immunostained for S100A2 and p53 proteins. Immunohistochemical staining patterns of S100A2 in the NSCLC tissue samples examined were either nuclear (nS100A2), cytoplasmic (cS100A2), or both. A significant association between nS100A2 positivity and better disease-free interval was observed (hazards ratio 0.47; 95% confidence interval 0.23–0.99; P = 0.047). Similarly, cS100A2 negativity was marginally associated with shorter overall survival (P = 0.07). Patients without lymphatic infiltration and an earlier disease stage had significantly better overall survival and disease-free interval. The S100A2 expression pattern in operable NSCLC varies widely, and this differential expression (nuclear, cytoplasmic or both) seems to correlate with prognosis. Intensity of expression was highest in the early and advanced stages, and equally distributed in the middle stages. This observation may be indicative of a dual role for this protein both during earlier and advanced disease stages, and may also explain the differential immunoexpression of S100A2. Analysis of the disease-free interval showed that nS100A2-negative and p53-positive expression was associated with a statistically significant (P = 0.003) shorter disease-free interval in comparison with nS100A2-positive and p53-negative expression (12 versus 30 months, respectively). Further studies are required to establish whether S100A2 protein may have a substantial role as a prognostic or predictive indicator in this unfavorable group of patients.

The role of omental transposition for the management of postoperative mediastinitis: a case series

IntroductionThe aim of our study is to present our experience from the management of six patients with deep sternal wood infection and mediastinitis after aortocoronary by pass grafting.Case seriesFive Caucasian Greek male patients and a Caucasian Greek female were subjected to aortocoronary by pass grafting. Mean time of sternal dehiscence and mediastinitis was 9–17 (mean 11) days. We managed these patients with total sternectomy and transposition of the greater omentum in the thorax. All patients had an uneventful postoperative course.ConclusionWe believe that greater omentum is the ideal reconstruction tissue for deep sternal wound infections and mediastinitis. Timely diagnosis, aggressive sternal debridement and omental flap coverage represent the mainstay of therapy in this highly lethal complication.

Simultaneously performed off-pump coronary artery bypass grafting and colectomy: a case report.

This is written so as to report the case of a 71-year-old male with a diagnosis of sigmoid adenocarcinoma accompanied by severe coronary artery disease and unstable angina, which was subject to simultaneous surgical treatment. The patient initially underwent an off-pump coronary artery revascularization in order to avoid the complications of cardiopulmonary bypass, providing the opportunity of a colectomy at the same time with the use of safe surgical means. Our case suggests that performing an off-pump bypass procedure prior to cancer surgery can be an appropriate course of action in carefully selected cases.