Human pericardial proteoglycan 4 (lubricin): Implications for postcardiotomy intrathoracic adhesion formation.

OBJECTIVE: Intrapericardial fibrous adhesions increase the risk of sternal reentry. Proteoglycan 4/lubricin (PRG4) is a mucin-like glycoprotein that lubricates tissue compartments and prevents inflammation. We characterized PRG4 expression in human pericardium and examined its effects in vitro on human cardiac myofibroblast fibrotic activity and in vivo as a measure of its therapeutic potential to prevent adhesions. METHODS: Full-length PRG4 expression was determined using Western blot analysis and amplified luminescent proximity homogeneous assay in human pericardial tissues obtained at cardiotomy. The in vitro effects of PRG4 were investigated on human cardiac myofibroblasts for cell adhesion, collagen gel contraction, and cell-mediated extracellular matrix remodeling. The influence of PRG4 on pericardial homeostasis was determined in a chronic porcine animal model. RESULTS: PRG4 is expressed in human pericardial fluid and colocalized with pericardial mesothelial cells. Recombinant human PRG4 prevented human cardiac myofibroblast attachment and reduced myofibroblast activity assessed using collagen gel contraction assay (64.6% ± 8.1% vs 47.1% ± 6.8%; P = .02). Using a microgel assay, human cardiac myofibroblast mediated collagen fiber remodeling was attenuated by PRG4 (1.17 ± 0.03 vs 0.90 ± 0.05; P = .002). In vivo, removal of pericardial fluid alone induced severe intrapericardial adhesion formation, tissue thickening, and inflammatory fluid collections. Restoration of intrapericardial PRG4 was protective against fibrous adhesions and preserved the pericardial space. CONCLUSIONS: For the first time, we show that PRG4 is expressed in human pericardial fluid and regulates local fibrotic myofibroblast activity. Loss of PRG4-enriched pericardial fluid after cardiotomy might induce adhesion formation. Therapeutic restoration of intrapericardial PRG4 might prevent fibrous/inflammatory adhesions and reduce the risk of sternal reentry.

High-dose, pulsatile erlotinib in two NSCLC patients with leptomeningeal metastases--one with a remarkable thoracic response as well.

A considerable number of patients with epidermal growth factor receptor (EGFR)-mutated non-small-cell lung cancer (NSCLC) develop leptomeningeal metastases. Leptomeningeal metastases are associated with deterioration of clinical symptoms and poor survival. Traditionally, treatment of metastases in the central nervous system consists of radiotherapy and less frequently, surgery. The role of systemic therapy is limited due to the blood-brain barrier inhibiting pharmacological doses to be reached in the central nervous system. Several case reports have described high-dose, pulsatile tyrosine kinase inhibitors as an effective treatment of leptomeningeal metastases, based on the hypothesis that higher concentrations in the cerebrospinal fluid can be reached by higher systemic concentrations. Here, we describe two patients with EGFR-mutated non-small cell lung cancer, with both clinical and radiological response to this high-dose, pulsatile regimen. Interestingly, one patient showed a remarkable response of intrathoracic response as well.

Adhesion barrier reduces postoperative adhesions after cardiac surgery.

Reoperation in cardiac surgery is associated with increased risk due to surgical adhesions. Application of a bioresorbable material could theoretically reduce adhesions and allow later development of a free dissection plane for cardiac reoperation. Twenty-one patients in whom a bioresorbable hyaluronic acid-carboxymethylcellulose adhesion barrier had been applied in a preceding surgery underwent reoperations, while 23 patients underwent reoperations during the same period without a prior adhesion barrier. Blinded observers graded the tenacity of the adhesions from surgical video recordings of the reoperations. No excessive bleeding requiring wound reexploration, mediastinal infection, or other complication attributable to the adhesion barrier occurred. Multiple regression analysis showed that shorter duration of the preceding surgery, non-use of cardiopulmonary bypass in the preceding surgery, and use of the adhesion barrier were significantly associated with less tenacious surgical adhesions. The use of a bioresorbable material in cardiac surgery reduced postoperative adhesions, facilitated reoperation, and did not promote complications. The use of adhesion barrier is recommended in planned staged procedures and those in which future reoperation is likely.

An observational study of CoSeal for the prevention of adhesions in pediatric cardiac surgery.

We sought to evaluate the utility and safety of CoSeal Surgical Sealant (Baxter) for the prevention of cardiac adhesions in children. Seven cardiac surgery centers in Europe recruited consecutive pediatric patients requiring primary sternotomy for staged repair of congenital heart defects. Exclusion criteria included immune system disorder, unplanned reoperation, or reoperation within three months of primary repair. CoSeal was sprayed onto the surface of the heart at the end of surgery. Evaluation of adhesions took place at first reoperation. Data on safety, duration of surgery, and ease of CoSeal use were also collected. Seventy-nine pediatric patients were recruited between February 2005 and September 2007. Of these, 76 underwent major surgery to repair a wide range of congenital heart defects. Thirty-six patients underwent reoperation >3 months after primary repair, and were included in the efficacy analysis. Mean adhesions score was 8.3 (standard deviation [S.D.] 2.4; range 7-16). Six adverse events (5 serious) were possibly/definitely attributed to CoSeal. CoSeal's ease of use at primary operation was graded by surgeons as 12.1 mm (S.D. 9.8) on a visual analog scale of 0 ('very easy') to 100 mm ('very difficult'). Results of this prospective uncontrolled trial justify further investigation in a randomized, controlled trial.

A simple method to prevent internal thoracic artery tension: a single pericardio-thoracic suture technique.

Tension on the internal mammary artery is a major risk for anastomosis in patients with severe emphysematous lungs. For this reason, it can be necessary to harvest the internal thoracic artery to its origin, to skeletonize it, or as a last resort to use it as a free graft. Sometimes, these maneuvers cannot be enough to solve the problem. A simple suture technique to hang up the pericardium to the chest wall is described that eliminates herniation of emphysematous lungs across mediastinum and reduces tension on the left internal mammary artery.

[Intrathoracic bleeding during video-assisted thoracoscopic lobectomy and segmentectomy].

We have reviewed our experience from January 2001 through January 2003 in 33 video-assisted thoracoscopic lobectomy and segmentectomy (VATS) in patients with cT1N0M0 lung cancer to look at intraoperative bleeding from pulmonary vessels. Intraoperative bleeding occurred in 15 cases, 45.5% of 33 VATS procedures, and 2 cases, 6.1% of VATS procedures converted to an open procedure. Intraoperative bleeding occurred more frequently in VATS segmentectomy than VATS lobectomy. Most of bleeding from pulmonary arteries and veins can be controlled by compression, and they can be controlled thoracoscopically by tie or suture through the utility thoracotomy. But, significant bleeding from pulmonary arteries, which can not be controlled with a mounted swab, it should be converted to an open procedure.

Reduction of retrosternal and pericardial adhesions with rapidly resorbable polymer films.

BACKGROUND: The formation of postoperative cardiac adhesions makes a repeat sternotomy time consuming and dangerous. Many attempts have been made to solve this problem by using either drugs to inhibit fibrinolytic activity or different types of pericardial substitutes. The results have not been satisfactory. METHODS: The efficacy of bioresorbable film prototypes made of polyethylene glycol (EO) and polylactic acid (LA) (EO/LA = 1.5, 2.5, and 3.0) in the prevention of adhesions after cardiac operations in canine models was tested. After desiccation and abrasion of the epicardium, a transparent bioresorbable film was placed over the heart. The pericardium was closed to allow intrapericardial adhesions (n = 32) or left open and attached to the chest wall to induce retrosternal adhesions (n = 17). Postoperative recovery was similar among the groups. Retrosternal and pericardial adhesions were evaluated at necropsy 3 weeks later by assessing area, tenacity, and density of the adhesions. RESULTS: In the control dogs, tenacious, dense adhesions were observed. In contrast, adhesion formation was reduced at all sites covered by the films. The bioresorbable films were efficacious in the reduction of adhesion formation between epicardium and pericardium or between epicardium and sternum after cardiac operation. The EO/LA 1.5 film most effectively prevented the early adhesions. CONCLUSIONS: The bioresorbable films (EO/LA = 1.5, 2.5, and 3.0) significantly reduced adhesion formation, with EO/LA = 1.5 (Repel CV) being optimal. As the barrier was rapidly resorbed, the capsule formation induced by permanent barriers was avoided.

Retrosternal fat pad for prevention of suppurative sternitis.

An increased incidence of postoperative sternal infection has been reported after the use of bilateral internal mammary arteries for coronary artery grafting. In this series, a pedicled pericardial fat pad was mobilized to lie in the retrosternal space before the sternum was approximated. This technique was used in 101 consecutive patients who underwent coronary artery grafting using bilateral internal mammary arteries. Twenty-four percent of the patients were diabetic. No suppurative sternitis developed in any of these patients.

Meta-analysis of antibiotics in tube thoracostomy.

The use of antibiotics for patients undergoing tube thoracostomy was determined to be highly variable based on a study conducted at a national meeting of surgeons. A meta-analysis of six randomized studies previously reported was performed. The analysis was carried out using the Confidence Profile Method software FAST*PRO. The meta-analysis was structured using dichotomous outcomes of infectious chest processes (empyema, effusion, pneumonia, wound infection, tracheitis, etc.) versus no infectious chest process in patients with and without antibiotics. The effect measures calculated included actual difference in probabilities, relative risk, percent differences in probabilities, and odds ratio. The results of this meta-analysis suggest that antibiotics should be used in patients undergoing tube thoracostomy. Antibiotic selection should maximize therapy for Staph. aureus. The implementation of this practice guideline will require the co-operation of multiple specialty oriented physicians and surgeons.

Iatroepidemics: a probe to examine systematic preventable errors in (chest) medicine.

Iatroepidemics are extreme examples of the inadequacies and errors that are prevalent in medicine. Their causes and evaluation are useful in demonstrating that medicine has a potentially destructive side as well as a highly constructive one. In the 1960s, the ATS left the sanitoria and joined the mainstream of medicine. In the 1980s it has become apparent that formal connections with science are not enough to ensure maximal safety for our patients. Nor are these connections sufficient to ensure maximal effectiveness of the measures we use to treat patients. A new awareness of our collective responsibility for improved patient outcome would be the obvious first step. Translating this sense of responsibility into new organizational approaches could place the ATS at the forefront of providing needed, and perhaps inevitable, reforms of medicine generally.