Tamas F. Molnar

What Are the Considerations in the Surgical Approach in Pulmonary Metastasectomy

There are four matters of uncertainty considered in this working group report, which are distilled into four clinical questions: (1) What is the evidence for the need for palpation of the lung in modern era of imaging? (2) Is there evidence of a difference in outcome for an open versus a closed approach? (3) Is there evidence of a difference in outcome for an initial policy of bilateral versus unilateral exploration? (4) In patients with known bilateral disease, is there a difference in outcome with a simultaneous versus a staged approach? We searched the literature formally and supplemented this with knowledge from all other sources. We provide evidence tables on the first two questions by relying on a group consensus and frame recommendations for the other two. There are no randomized trials to guide us but there are comparative studies addressing the need for palpation and the need to and open operation in all cases. The evidence is equivocal, and opinions are divided in the literature. Palpation of the lung is still seen as necessary in a therapeutic metastasectomy as opposed to a diagnostic procedure when videothoracoscopy is adequate. However, the importance of palpation becomes less clear with advances in imaging. Routine bilateral exploration for unilateral disease was not favored. For bilateral disease, an initial median sternotomy has a place for some cases but sequenced thoracotomy was preferred.

Down-regulation of canonical and up-regulation of non-canonical Wnt signalling in the carcinogenic process of squamous cell lung carcinoma.

The majority of lung cancers (LC) belong to the non-small cell lung carcinoma (NSCLC) type. The two main NSCLC sub-types, namely adenocarcinoma (AC) and squamous cell carcinoma (SCC), respond differently to therapy. Whereas the link between cigarette smoke and lung cancer risk is well established, the relevance of non-canonical Wnt pathway up-regulation detected in SCC remains poorly understood. The present study was undertaken to investigate further the molecular events in canonical and non-canonical Wnt signalling during SCC development. A total of 20 SCC and AC samples with matched non-cancerous controls were obtained after surgery. TaqMan array analysis confirmed up-regulation of non-canonical Wnt5a and Wnt11 and identified down-regulation of canonical Wnt signalling in SCC samples. The molecular changes were tested in primary small airway epithelial cells (SAEC) and various lung cancer cell lines (e.g. A549, H157, etc). Our studies identified Wnt11 and Wnt5a as regulators of cadherin expression and potentiated relocation of β-catenin to the nucleus as an important step in decreased cellular adhesion. The presented data identifies additional details in the regulation of SCC that can aid identification of therapeutic drug targets in the future.

Non-malignant tracheo-gastric fistula following esophagectomy for cancer

Two cases of neoesophago-tracheal fistula are described. After esophagectomy for cancer a fistula developed between the trachea and the pulled-up stomach probably because of the ischaemic effect of the tracheostomy tube. At single stage repairs, the fistulae were divided and the gastric defects were closed directly. In one case, tracheal resection and anastomosis was necessary. The defect on the membranous trachea in both cases was patched with an autologous fascia lata graft. A left pectoralis major muscle flap was interposed between the suture lines to prevent recurrence of the fistula. Treatment of this potentially life-threatening and rare condition yielded excellent results.

Pulmonary enteric adenocarcinoma indistinguishable morphologically and immunohistologically from metastatic colorectal carcinoma

Adenocarcinoma is the most common and heterogeneous type of lung cancer. Pulmonary enteric adenocarcinoma (PEAC) is a recently described, extremely rare primary pulmonary adenocarcinoma variant, which has a histological morphology and immunohistochemical phenotype similar to metastatic colorectal carcinoma (MCC). It was described originally in 1991 by Tsao et al. as a primary pulmonary adenocarcinoma with enteric differentiation. In 2005, Inamura et al. reported a series of seven cases, and in 2008 Meada et al. described a case as pulmonary intestinal-type adenocarcinoma. Currently, there have only been 17 reported cases. PEAC was classified as a rare variant of invasive adenocarcinoma by the International Association for the Study of Lung Cancer/American Thoracic Respiratory Society in 2011. Here we describe a PEAC that developed in the postoperative scar of a 65-year-old male with a history of segmental resection and adjuvant radiotherapy for squamous cell carcinoma (SCC). Together, retrospective comparative analysis of tumour samples from the first and second surgical interventions and the autopsy findings suggest that the subsequent adenocarcinoma was PEAC rather than metastatic adenocarcinoma. The tumour was indistinguishable from MCC by histology, immunohistochemistry and EGFR/K-RAS mutation analysis.

Surgical Management of Chest Wall Trauma

Recent paradigm shift in major trauma profile elevates chest wall injuries among the most important topics of the specialty. Due to mass casualties of terror attacks and asymmetric warfare, civilian and military trauma care challenges thoracic surgery, traumatology, intensive anesthesiology, and related specialties. Contemporary advances of the main issues are systemically presented and discussed, such as soft tissue and bony structure injuries, complex traumas like flail chest, and extensively destroyed chest wall.

Tissue engineering and biotechnology in general thoracic surgery.

Public interest in the recent progress of tissue engineering, a special line of biotechnology, makes the current review on thoracic surgery highly relevant. In this article, techniques, materials and cellular processes are discussed alongside their potential applications in tissue repair. Different applications of tissue engineering in tracheo-bronchial replacement, lung tissue cultures and chest-wall reconstruction are also summarised in the article. Potential tissue engineering-based solutions for destructive, chronic lung-injury-related conditions and replacement of tubular structures in the central airways are also examined.

Expression of the somatostatin receptor subtype 4 in intact and inflamed pulmonary tissues.

Somatostatin released from capsaicin-sensitive sensory nerves of the lung during endotoxin-induced murine pneumonitis inhibits inflammation and hyperresponsiveness, presumably via somatostatin receptor subtype 4 (sst4). The goal of the present study was to identify sst4 receptors in mouse and human lungs and to reveal its inflammation-induced alterations with real-time quantitative PCR, Western blot, and immunohistochemistry. In non-inflamed mouse and human lungs, mRNA expression and immunolocalization of sst4 are very similar. They are present on bronchial epithelial, vascular endothelial, and smooth-muscle cells. The sst4 receptor protein in the mouse lung significantly increases 24 hr after intranasal endotoxin administration as well as in response to 3 months of whole-body cigarette smoke exposure, owing to the infiltrating sst4-positivite mononuclear cells and neutrophils. In the chronically inflamed human lung, the large number of activated macrophages markedly elevate sst4 mRNA levels, although there is no change in acute purulent pneumonia, in which granulocytes accumulate. Despite mouse granulocytes, human neutrophils do not show sst4 immunopositivity. We provide the first evidence for the expression, localization, and inflammation-induced alterations of sst4 receptors in murine and human lungs. Inasmuch as tissue distribution of this receptor is highly similar, extrapolation of murine experimental results to human conditions might be possible.

Gastroesophageal reflux disease and non‐small cell lung cancer. Results of a pilot study

The sharp rise in the frequency of adenocarcinoma and relative decrease of squamous cell carcinoma of the respiratory and digestive systems, raises suspicion of a common element in their carcinogenetic cascade, which could result in similar trends in cell-type distribution changes of esophageal and lung cancers. The possible role of chemical irritation caused by gastroesophageal reflux disease (GERD) in non-small cell lung cancer (NSCLC) patients was investigated. There was no significant difference between the adenocarcinoma and the squamous cell carcinoma groups, neither in the composite DeMeester scores nor in any of the separate parameters of the complex score investigated. However, the ratio of detected gastroesophageal reflux cases was considerably higher than in the average population. This factor may be one element of a multifactorial cancer promotion.

Increased Wnt5a in squamous cell lung carcinoma inhibits endothelial cell motility

BackgroundAngiogenesis is important both in normal tissue function and disease and represents a key target in lung cancer (LC) therapy. Unfortunately, the two main subtypes of non-small-cell lung cancers (NSCLC) namely, adenocarcinoma (AC) and squamous cell carcinoma (SCC) respond differently to anti-angiogenic e.g. anti-vascular endothelial growth factor (VEGF)-A treatment with life-threatening side effects, often pulmonary hemorrhage in SCC. The mechanisms behind such adverse reactions are still largely unknown, although peroxisome proliferator activator receptor (PPAR) gamma as well as Wnt-s have been named as molecular regulators of the process. As the Wnt microenvironments in NSCLC subtypes are drastically different, we hypothesized that the particularly high levels of non-canonical Wnt5a in SCC might be responsible for alterations in blood vessel growth and result in serious adverse reactions.MethodsPPARgamma, VEGF-A, Wnt5a, miR-27b and miR-200b levels were determined in resected adenocarcinoma and squamous cell carcinoma samples by qRT-PCR and TaqMan microRNA assay. The role of PPARgamma in VEGF-A expression, and the role of Wnts in overall regulation was investigated using PPARgamma knock-out mice, cancer cell lines and fully human, in vitro 3 dimensional (3D), distal lung tissue aggregates. PPARgamma mRNA and protein levels were tested by qRT-PCR and immunohistochemistry, respectively. PPARgamma activity was measured by a PPRE reporter system. The tissue engineered lung tissues expressing basal level and lentivirally delivered VEGF-A were treated with recombinant Wnts, chemical Wnt pathway modifiers, and were subjected to PPARgamma agonist and antagonist treatment.ResultsPPARgamma down-regulation and VEGF-A up-regulation are characteristic to both AC and SCC. Increased VEGF-A levels are under direct control of PPARgamma. PPARgamma levels and activity, however, are under Wnt control. Imbalance of both canonical (in AC) and non-canonical (in SCC) Wnts leads to PPARgamma down-regulation. While canonical Wnts down-regulate PPARgamma directly, non-canonical Wnt5a increases miR27b that is known regulator of PPARgamma.ConclusionDuring carcinogenesis the Wnt microenvironment alters, which can downregulate PPARgamma leading to increased VEGF-A expression. Differences in the Wnt microenvironment in AC and SCC of NSCLC lead to PPARgamma decrease via mechanisms that differentially alter endothelial cell motility and branching which in turn can influence therapeutic response.

Complications after ultrasonic lung parenchyma biopsy: a strong note for caution

BackgroundThis study aimed to determine the possible cause for an unacceptable frequency of postresectional pneumothorax in cases of ultrasonic scalpel use without a further reinforcing maneuver in lung biopsy during video-assisted thoracic surgery (VATS).MethodsData for a series of 16 consecutive VATS lung biopsy patients (group A) in which a disturbingly high number of minor and medium complications occurred were compared with data for a group of 20 patients previously subject to the same ultrasonic lung biopsy method (group B) without complication.ResultsThe two groups were identical in terms of all significant factors considered in relation to ultrasonic scalpel biopsy. Six notable air leakage complications occurred among the 16 patients of group A. One patient needed redrainage while still in the hospital. Two other patients required readmission and redrainage. In 4 of the 16 cases, late pneumothorax was detected after a “silent” 48-h postoperative period prolonging their hospital stay. Altogether, three medium complications occurred in group A, as compared with none in group B. The drainage duration in group B was not significantly shorter than in group A . Multivariate analysis showed a significant difference in complications favoring group B (odds ratio, 1.88).ConclusionsA high postoperative air leakage rate was observed in a simple case series using an unsecured harmonic scalpel after a randomized trial of the same method in the same institute with a diametrically opposite outcome. The medium complication rate of 3 in 16 cases is unacceptable for a minor procedure such as lung biopsy. The two groups differed only in their thromboembolic prophylaxis protocol. Therefore, it is hypothesized that the recent introduction of low-molecular-weight heparin from day 1 may influence the complication rate. The authors’ observation calls for caution in use of the harmonic scalpel on lung tissue without reinforcing maneuvers (i.e., stitches or clips). To avoid unnecessary complications, operative technique adjustment is recommended.