Gregor J. Kocher

Diffuse descending necrotizing mediastinitis: surgical therapy and outcome in a single-centre series

OBJECTIVES Descending necrotizing mediastinitis (DNM) is a rare but rapidly progressing disease with a potentially fatal outcome, originating from odontogenical or cervical infections. The aim of this article was to give an up-to-date overview on this still underestimated disease, to draw the clinicians attention and particularly to highlight the need for rapid diagnosis and adequate surgical treatment. METHODS We present a retrospective analysis of 17 patients diagnosed and treated for advanced DNM between 1999 and 2011 in a tertiary referral medical centre. Hence, this is one of the largest single-centre studies in recent years concerning the diffuse form (i.e. extending into the lower mediastinum) of DNM. Subsequently, we analysed and compared the international literature with our data, with the focus on surgical management and outcome. RESULTS In our series of 17 adult patients, 16 were surgically treated by median sternotomy (n = 8) or the clamshell (n = 8) approach for diffuse DNM. One patient, referred with septic shock, died 2 days after surgery. The median interval from diagnosis of DNM by cervicothoracic computed tomography scan and thoracic surgery was 6 h (range 1-24 h) in all but the one patient with fatal outcome (48 h). Concomitant cervicotomy was performed in 11 patients (65%) and tracheotomy in 9 (53%). The median duration of hospitalization was 16 days (range 4-50 days), including an intensive care unit stay of 4 days (range 1-50 days). CONCLUSIONS For DNM limited to the upper part of the mediastinum, which applies to the majority of cases, a transcervical approach and drainage may be sufficient. In advanced disease, extending below the tracheal carina, an immediate and more aggressive surgical approach is required to combat a much higher morbidity and mortality in this subset of patients. A timely situational approach via median sternotomy or a clamshell incision allowed us to maintain a very low morbidity, mortality and rate of reoperations, without major complications due to the surgical approach itself.

Blocking the epithelial-to-mesenchymal transition pathway abrogates resistance to anti-folate chemotherapy in lung cancer

Anticancer therapies currently used in the clinic often can neither eradicate the tumor nor prevent disease recurrence due to tumor resistance. In this study, we showed that chemoresistance to pemetrexed, a multi-target anti-folate (MTA) chemotherapeutic agent for non-small cell lung cancer (NSCLC), is associated with a stem cell-like phenotype characterized by an enriched stem cell gene signature, augmented aldehyde dehydrogenase activity and greater clonogenic potential. Mechanistically, chemoresistance to MTA requires activation of epithelial-to-mesenchymal transition (EMT) pathway in that an experimentally induced EMT per se promotes chemoresistance in NSCLC and inhibition of EMT signaling by kaempferol renders the otherwise chemoresistant cancer cells susceptible to MTA. Relevant to the clinical setting, human primary NSCLC cells with an elevated EMT signaling feature a significantly enhanced potential to resist MTA, whereas concomitant administration of kaempferol abrogates MTA chemoresistance, regardless of whether it is due to an intrinsic or induced activation of the EMT pathway. Collectively, our findings reveal that a bona fide activation of EMT pathway is required and sufficient for chemoresistance to MTA and that kaempferol potently regresses this chemotherapy refractory phenotype, highlighting the potential of EMT pathway inhibition to enhance chemotherapeutic response of lung cancer.

Human lung-derived mesenchymal stem cell-conditioned medium exerts in vitro antitumor effects in malignant pleural mesothelioma cell lines

BackgroundThe soluble factors secreted by mesenchymal stem cells are thought to either support or inhibit tumor growth. Herein, we investigated whether the human lung-derived mesenchymal stem cell-conditioned medium (hlMSC-CM) exerts antitumor activity in malignant pleural mesothelioma cell lines H28, H2052 and Meso4.MethodshlMSC-CM was collected from the human lung-derived mesenchymal stem cells. Inhibition of tumor cell growth was based on the reduction of cell viability and inhibition of cell proliferation using the XTT and BrdU assays, respectively. Elimination of tumor spheroids was assessed by the anchorage-independent sphere formation assay. The cytokine profile of hlMSC-CM was determined by a chemiluminescence-based cytokine array.ResultsOur data showed that hlMSC-CM contains a broad range of soluble factors which include: cytokines, chemokines, hormones, growth and angiogenic factors, matrix metalloproteinases, metalloproteinase inhibitors and cell–cell mediator proteins. The 48- and 72-hour hlMSC-CM treatments of H28, H2052 and Meso4 cell lines elicited significant decreases in cell viability and inhibited cell proliferation. The 72-hour hlMSC-CM incubation of H28 cells completely eliminated the drug-resistant sphere-forming cells, which is more potent than twice the half maximal inhibitory concentration of cisplatin.ConclusionsOur findings indicate that the cell-free hlMSC-CM confers in vitro antitumor activities via soluble factors in the tested mesothelioma cells and, hence, may serve as a therapeutic tool to augment the current treatment strategies in malignant pleural mesothelioma.

Low‐Dose Irinotecan Improves Advanced Lupus Nephritis in Mice Potentially by Changing DNA Relaxation and Anti–Double‐Stranded DNA Binding

Despite clear advances in the treatment of systemic lupus erythematosus (SLE), many patients still present with refractory lupus nephritis, requiring new treatment strategies for this disease. This study was undertaken to determine whether reduced doses of the topoisomerase I (topo I) inhibitor irinotecan, which is known as a chemotherapeutic agent, suppress SLE in (NZB × NZW)F1 (NZB/NZW) mice, and to evaluate the potential mechanism by which irinotecan influences the course of SLE.

Lessons from a large trauma center: impact of blunt chest trauma in polytrauma patients—still a relevant problem?

BackgroundThoracic trauma is the third most common cause of death after abdominal injury and head trauma in polytrauma patients. The purpose of this study was to investigate epidemiological data, treatment and outcome of polytrauma patients with blunt chest trauma in order to help improve management, prevent complications and decrease polytrauma patients’ mortality.MethodsIn this retrospective study we included all polytrauma patients with blunt chest trauma admitted to our tertiary care center emergency department for a 2-year period, from June 2012 until May 2014. Data collection included details of treatment and outcome. Patients with chest trauma and Injury Severity Score (ISS) ≥18 and Abbreviated Injury Scale (AIS) >2 in more than one body region were included.ResultsA total of 110 polytrauma patients with blunt chest injury were evaluated. 82 of them were males and median age was 48.5 years. Car accidents, falls from a height and motorbike accidents were the most common causes (>75%) for blunt chest trauma. Rib fractures, pneumothorax and pulmonary contusion were the most common chest injuries. Most patients (64.5%) sustained a serious chest injury (AISthorax 3), 19.1% a severe chest injury (AISthorax 4) and 15.5% a moderate chest injury (AISthorax 2). 90% of patients with blunt chest trauma were treated conservatively. Chest tube insertion was indicated in 54.5% of patients. The need for chest tube was significantly higher among the AISthorax 4 group in comparison to the AIS groups 3 and 2 (p < 0.001). Also, admission to the ICU was directly related to the severity of the AISthorax (p < 0.001). The severity of chest trauma did not correlate with ICU length of stay, intubation days, complications or mortality.ConclusionAlthough 84.5% of patients suffered from serious or even severe chest injury, neither in the conservative nor in the surgically treated group a significant impact of injury severity on ICU stay, intubation days, complications or mortality was observed. AISthorax was only related to the rate of chest tube insertions and ICU admission. Management with early chest tube insertion when necessary, pain control and chest physiotherapy resulted in good outcome in the majority of patients.

Repair of sternoclavicular joint dislocations with FiberWire

PurposeUp to 50% of traumatic sternoclavicular joint (SCJ) dislocations need open reduction and fixation to prevent long-term complications and complaints. We present our preferred surgical approach for acute as well as chronic SCJ dislocations, including their outcome.MethodsFive consecutive male patients with a median age of 27 (range 20–49) were treated for traumatic anterior (n = 2) or posterior (n = 3) SCJ dislocation. Open reduction and surgical fixation were achieved by a modified figure-of-eight sutures using Fiberwire®. In anterior dislocations, an additional reconstruction of the costoclavicular ligament was performed. Median follow-up was 11 months (range 9–48) and included clinical evaluation and the use of the DASH questionnaire.ResultsOpen surgical reduction and SCJ repair were successfully achieved in all patients without complications. Repair resulted in very good functional outcomes in all five patients with DASH scores of 0, 8 (n = 3) and 5, 8 (n = 2), respectively.ConclusionsThe presented technique allowed simple, effective, and durable repair of the SCJ joint in patients with SCJ dislocations with excellent functional outcomes.

True aneurysm of the peripheral pulmonary artery due to necrotizing giant cell arteritis

Pulmonary artery aneurysm in adults is a rare diagnosis. Most cases described in the literature are either associated with congenital heart disease or pulmonal arterial hypertension, respectively, or are not true aneurysms but rather pseudoaneurysms, which are usually iatrogenic. We present the case of a 68-year old female patient with the incidental finding of a true aneurysm of the right peripheral pulmonary artery with a maximum diameter of 4 cm. With increasing aneurysm diameter over time, the decision for a surgical resection was made. Complete resection of the aneurysm including lower lobe resection was performed. Histopathological examination showed necrotizing giant cell arteritis as the underlying cause. The postoperative course was uneventful and no signs of further disease activity were detected. To our knowledge, this is the first reported case of a pulmonary artery aneurysm caused by giant cell arteritis, whereas it should be noted that the distinction between Takayasu arteritis and giant cell arteritis is not clearly defined. Considering the high mortality associated with aneurysm rupture, surveillance is advocated for small aneurysms, whereas for larger aneurysms and those showing signs of progression in size despite medical therapy or even dissection, surgical intervention should be considered.

Single-cannula, single-incision thoracoscopic anatomic segmentectomy after pneumonectomy

From the Division of General Thoracic Surgery, and Departments of Anesthesiology and Pain Therapy and Cardiovascular Surgery, Bern University Hospital, University of Bern, Bern, Switzerland. Disclosures: Authors have nothing to disclose with regard to commercial support. Received for publication Jan 24, 2017; revisions received March 23, 2017; accepted for publication March 28, 2017; available ahead of print April 25, 2017. Address for reprints: Gregor J. Kocher, MD, Division of General Thoracic Surgery, University Hospital Bern, Bern CH – 3010, Switzerland (E-mail: gregor.kocher@insel.ch). J Thorac Cardiovasc Surg 2017;154:e29-31 0022-5223/

IgG4-related disease of the lung: a rare differential diagnosis to lung cancer after positive positron emission tomography and biopsy

36.00 Copyright 2017 by The American Association for Thoracic Surgery http://dx.doi.org/10.1016/j.jtcvs.2017.03.127 Dual-lumen venovenous ECMO cannula in the right internal jugular vein.

Single-incision thoracoscopic right pneumonectomy with primary division of the pulmonary artery

Immunoglobulin G4-related disease is a rare immune-mediated condition that often causes serious diagnostic problems. Symptoms are unspecific, and several organs can be involved. To date, IgG4-related lung disease has seldom been reported in literature. Nevertheless, a variety of pulmonary involvement has been described, which can mimic malignancy. The gold standard for the diagnosis is the identification of typical histopathological features, even if diagnostic biomarker such as serum IgG4 concentration can be an indicator for a more aggressive course of the disease.