Video-assisted thoracoscopic lobectomy: which patients require postoperative physiotherapy?

OBJECTIVES: Following major thoracic surgery physiotherapy is recommended to improve reduced lung volume, aid secretion clearance, and improve mobility, however, in many centres physiotherapy provision is variable following minimally invasive video-assisted thoracoscopic surgery (VATS). The objective of this study was to observe frequency of problems potentially amenable to physiotherapy following VATS lobectomy, and to identify associated baseline factors of patients in whom physiotherapy may be beneficial. METHODS: A prospective observational study was performed including all consecutive cancer patients undergoing VATS lobectomy in a regional centre over 4years (2012-2016). Standard postoperative care included early mobilisation by nursing staff from postoperative day one (POD1). Physiotherapy assessment of all patients on POD1 determined presence of issues potentially amenable to physiotherapy intervention, and treatment was commenced. Outcome measures included postoperative pulmonary complication (PPC) development, hospital and high dependency unit (HDU) length of stay (LOS). RESULTS: Of 285 patients, 209 (73%) received physiotherapy to assist/improve reduced mobility, of these 23 (8%) also received sputum clearance therapies and 65 (23%) specific therapy for lung volume loss. The remaining 76 (27%) patients had significantly lower hospital/HDU LOS (P<0.001) reflecting uncomplicated recovery. Chronic obstructive pulmonary disease (COPD), body mass index (BMI), preoperative mobility and age were independently associated with issues potentially amenable to physiotherapy (P=0.013). CONCLUSION: Following VATS lobectomy a large proportion of patients demonstrated issues potentially amenable to physiotherapy. The authors recommend that patients receive routine physiotherapy assessment following this type of surgery to ensure that all issues are identified early. Screening of COPD, BMI, preoperative mobility and age will allow early identification of patients who may benefit most from postoperative physiotherapy and preoperative optimisation, however, these factors cannot predict the need for physiotherapy.

Inhibiting MYC binding to the E-box DNA motif by ME47 decreases tumour xenograft growth.

Developing therapeutics to effectively inhibit the MYC oncoprotein would mark a key advance towards cancer patient care as MYC is deregulated in over 50% of human cancers. MYC deregulation is correlated with aggressive disease and poor patient outcome. Despite strong evidence in mouse models that inhibiting MYC would significantly impact tumour cell growth and patient survival, traditional approaches have not yet yielded the urgently needed therapeutic agents that directly target MYC. MYC functions through its interaction with MAX to regulate gene transcription by binding to E-box DNA response elements of MYC target genes. Here we used a structure-based strategy to design ME47, a small minimalist hybrid protein (MHP) able to disrupt the MAX:E-box interaction/binding and block transcriptional MYC activity. We show that inducing ME47 expression in established tumour xenografts inhibits tumour growth and decreases cellular proliferation. Mechanistically, we show by chromatin immunoprecipitation that ME47 binds to E-box binding sites of MYC target genes. Moreover, ME47 occupancy decreases MYC:DNA interaction at its cognate E-box binding sites. Taken together, ME47 is a prototypic MHP inhibitor that antagonizes tumour cell growth in vitro and in vivo and inhibits the interaction of MYC with DNA E-box elements. These results support ME47's role as a MYC inhibitor and suggest that MHPs provide an alternative therapeutic targeting system that can be used to target transcription factors important in human diseases, including cancer.

Tracheo-oesophageal fistula in a patient with chronic sarcoidosis.

Sarcoidosis is a common multisystem granulomatous condition of unknown aetiology, predominantly involving the respiratory system. Tracheal stenosis has been described but we believe that we present the first case of a tracheo-oesophageal fistula secondary to chronic sarcoidosis. A 57-year-old woman with sarcoidosis, a known tracheal stricture and a Polyflex(®) stent in situ presented with stridor. Bronchoscopy confirmed in-stent stenosis, by exuberant granulation tissue. The stent was removed and the granulation tissue was resected accordingly. Postoperatively, the patient was noticed to have an incessant cough and video fluoroscopy raised the suspicion of a tracheo-oesophageal fistula. A repeat bronchoscopy demonstrated marked granulation tissue, accompanied by a fistulous connection with the oesophagus at the mid-lower [middle of the lower] third of the trachea. Three Polyflex(®) stents were sited across the entire length of the trachea. Sarcoidosis presents with varying clinical manifestations and disease progression. Tracheal involvement appears to be a rare phenomenon and usually results in stenosis. To date, there has been little or no documented literature describing the formation of a tracheo-oesophageal fistula resulting from sarcoidosis. Early reports documented the presence of sarcoidosis induced weakening in the tracheal wall, a process termed tracheal dystonia. Weaknesses are more apparent in the membranous aspect of the trachea. Despite the rare nature of such pathology, this case report highlights the need to consider the presence of a tracheo-oesophageal fistula in sarcoidosis patients presenting with repeat aspiration in the absence of an alternate pathology.

MYC activity is negatively regulated by a C-terminal lysine cluster.

The MYC oncogene is not only deregulated in cancer through abnormally high levels of expression, but also through oncogenic lesions in upstream signalling cascades. Modelling MYC deregulation using signalling mutants is a productive research strategy. For example, the MYC threonine-58 to alanine substitution mutant (T58A) within MYC-homology box 1 is more transforming than wild-type (WT) MYC, because of decreased apoptosis and increased protein stability. Understanding the regulatory mechanisms controlling T58 phosphorylation has led to new approaches for the development of MYC inhibitors. In this manuscript, we have extensively characterized a MYC signalling mutant in which six lysine residues near the highly conserved MYC homology box IV and basic region have been substituted to arginines (6KR). Previous literature suggests these lysines can undergo both ubiquitylation and acetylation. We show MYC 6KR is able to fully rescue the slow growth phenotype of HO15.19 MYC-null fibroblasts, and promote cell cycle entry of serum-starved MCF10A cells. Remarkably, 6KR increased anchorage-independent colony growth compared with WT MYC in both SH-EP and MCF10A cells. Moreover, it was also more potent in promoting xenograft tumour growth of Rat1A and SH-EP cells. Combined, our data identify this region and these six lysines as important residues for the negative regulation of MYC-induced transformation. Mechanistically, we demonstrate that, unlike T58A, the increased transformation is not a result of increased protein stability or a reduced capacity for 6KR to induce apoptosis. Through expression analysis and luciferase reporter assays, we show that 6KR has increased transcriptional activity compared with WT MYC. Combined, through a comprehensive evaluation across multiple cell types, we identify an important regulatory region within MYC. A better understanding of the full scope of signalling through these residues will provide further insights into the mechanisms contributing to MYC-induced tumorigenesis and may unveil novel therapeutic strategies to target Myc in cancer.

Comparison of recognition tools for postoperative pulmonary complications following thoracotomy.

OBJECTIVES: To evaluate the recognition of postoperative pulmonary complications (PPC) following thoracotomy and lung resection using three PPC scoring tools. DESIGN: Prospective observational study. SETTING: Regional thoracic centre. PARTICIPANTS: One hundred and twenty-nine consecutive thoracotomy and lung resection patients (October 2007 and April 2008). MAIN OUTCOME MEASURES: PPC assessment was performed on a daily basis using three sets of criteria described by Brooks-Brunn, Gosselink et al. and Reeve et al.: the Brooks-Brunn Score (BBS), Gosselink Score (GS) and Melbourne Group Scale (MGS), respectively. The results were compared with treatment for PPC and clinical outcomes including mortality, postoperative length of stay and high dependency unit length of stay. RESULTS: PPC frequency was 13% (17/129) with the MGS, 6% (8/129) with the GS and 40% (51/129) with the BBS. The clinically observed incidence of treated (requiring antibiotic therapy or bronchoscopy) PPC was 12% (16/129). CONCLUSION: PPC treatment following thoracotomy is common. Of the three scoring tools, the MGS outperforms the BBS and the GS in terms of PPC recognition following thoracotomy and lung resection. Patients with a PPC-positive MGS score have a worse outcome as defined by mortality, high dependency unit length of stay and postoperative length of stay. The MGS is an easy-to-use multidisciplinary scoring tool, but further work is required into its use in minimally invasive surgery and in targeting high-risk groups for therapy.

Postoperative pulmonary complications following thoracic surgery: are there any modifiable risk factors?

BACKGROUND: Postoperative pulmonary complications (PPC) are the most frequently observed complications following lung resection, of which pneumonia and atelectasis are the most common. PPCs have a significant clinical and economic impact associated with increased observed number of deaths, morbidity, length of stay and associated cost. The aim of this study was to assess the incidence and impact of PPCs and to identify potentially modifiable independent risk factors. METHODS: A prospective observational study was carried out on all patients following lung resection via thoracotomy in a regional thoracic centre over 13 months. PPC was assessed using a scoring system based on chest x-ray, raised white cell count, fever, microbiology, purulent sputum and oxygen saturations. RESULTS: Thirty-four of 234 subjects (14.5%) had clinical evidence of PPC. The PPC patient group had a significantly longer length of stay (LOS) in hospital, high dependency unit (HDU) LOS, higher frequency of intensive care unit (ITU) admission and a higher number of hospital deaths. Older patients, body mass index (BMI) > or =30 kg/m(2), preoperative activity <400 m, American Society of Anesthesiologists (ASA) score > or =3, smoking history, chronic obstructive pulmonary disease (COPD), lower preoperative forced expiratory volume in 1 s (FEV(1)) and predicted postoperative (PPO) FEV(1) were all significantly (p<0.05) associated with PPC on univariate analysis. Multivariate analysis confirmed that age >75 years, BMI > or =30 kg/m(2), ASA > or =3, smoking history and COPD were significant independent risk factors in the development of PPC (p<0.05). CONCLUSION: The clinical impact of PPCs is marked. Significant independent preoperative risk factors have been identified in current clinical practice. Potentially modifiable risk factors include BMI, smoking status and COPD. The impact of targeted therapy requires further evaluation.

Necrotizing fasciitis of chest wall complicating empyema thoracis.

Necrotizing fasciitis affecting the chest wall is a rare condition and carries high mortality. It spreads rapidly, requiring early diagnosis and immediate extensive surgical debridement. The case of a 32 year old man afflicted with this uncommon condition following tube thoracostomy for empyema thoracis is described and literature reviewed.

Management of aortobronchial fistula following coarctation repair.

Aortobronchial fistula is a rare complication following thoracic aortic operations and is invariably fatal if not promptly diagnosed and repaired. Direct prosthetic repair carries a risk of graft repair sepsis and fistula recurrence. We describe two cases presenting with aortobronchial fistula following coarctation repair which were successfully treated by different surgical approaches.

Global myocardial revascularization without cardiopulmonary bypass using innovative techniques for myocardial stabilization and perfusion.

BACKGROUND: In off-pump coronary bypass grafting (CABG), invasiveness is reduced but technically perfect anastomosis is jeopardized by cardiac motion and the need to hurry to reduce the time of ischemia. Also, a major cause of postoperative morbidity and mortality is ungrafted circumflex coronary artery disease. We have devised a means of overcoming these shortcomings and performing multivessel CABG. The objective of this study was to assess the safety and efficacy of our technique. METHODS: One hundred patients with severe triple-vessel disease underwent multivessel off-pump CABG. For cardiac stabilization, a combination of local pericardial stabilization sutures and lifting and rotating the heart by means of posterior pericardial sutures were used. For myocardial perfusion, a technique of retrograde coronary sinus perfusion by arterial blood from the ascending aorta was used. RESULTS: Each patient received an average of 3.8 grafts (range 3 to 5). Complications included conversion to cardiopulmonary bypass (CPB) in 1 patient and a perioperative myocardial infarction in the same patient. In all other patients we were able to perform a satisfactory grafting in all territories with no operative mortality. Rapid recovery allowed 95% of our patients to resume normal activity within 1 month. A predischarge graft angiogram in 35 patients showed 97.8% patency. CONCLUSIONS: These results suggest that off-pump CABG with our techniques is effective and safe. Early clinical outcome and excellent patency rates suggest its more widespread use in selected cases.

One-stage surgical procedure for bilateral lung and liver hydatid cysts.

BACKGROUND: Echinococcus disease is endemic in areas where livestock are raised in association with dogs. The majority of patients reporting in the Department of Cardiovascular and Thoracic Surgery at Postgraduate Institute of Medical Education and Research have unilateral pulmonary hydatid disease. METHODS: From March 1988 to May 1996 we came across 58 patients with pulmonary hydatidosis, of which 5 patients presented with combined bilateral pulmonary and hepatic hydatid cysts. In these patients, to avoid three-stage operation of two thoracotomies and a laparotomy, we proceeded with simultaneous combined resection of hydatid cysts in one stage through midsternotomy along with laparotomy or transdiaphragmatic removal of liver cysts. RESULTS: Results indicate that combined resection of pulmonary and hepatic hydatid cysts is feasible with minimum morbidity and no recurrence. CONCLUSIONS: We conclude that a one-stage surgical procedure for bilateral lung and liver hydatid cysts is superior to the classic three-stage approach as it decreases morbidity, hospital stay, and cost.