Innes Y.P. Wan

Avoiding cardiopulmonary bypass in multivessel CABG reduces cytokine response and myocardial injury

BACKGROUND Proinflammatory cytokines play a key role in the inflammatory cascade after cardiopulmonary bypass and may induce cardiac dysfunction. We compared the production of cytokines and the degree of postoperative myocardial injury in patients with multivessel coronary artery disease undergoing coronary artery bypass grafting through median sternotomy with or without cardiopulmonary bypass. METHODS Forty-four consecutive patients were studied. Patients were selected for off-pump coronary artery bypass grafting whenever complete revascularization was technically feasible. There were no differences between the two groups with respect to age, sex, symptoms, or functional class. Plasma levels of tumor necrosis factor-alpha, interleukin (IL)-6, IL-8, and IL-10 were measured before the operation, at the end of the procedure, and 2, 4, 8, 24, and 48 hours thereafter. Levels of the MB isoenzyme of creatine kinase and cardiac troponin-I were also measured after the operation. RESULTS The number of grafts was 2+/-0.7 in the off-pump group (n = 18) and 3+/-0.8 in the cardiopulmonary bypass group (n = 26). There were no deaths or major complications in either group. Levels of tumor necrosis factor-alpha were low in both groups. No significant intergroup differences were noted regarding serial IL-6 measurements. However, IL-8 and IL-10 levels after the operation were lower in the off-pump group (IL-8, 4+/-1 versus 38+/-12 pg/mL, p < 0.01; IL-10, 5+/-2 versus 191+/-33 pg/mL, p < 0.001). Whereas postoperative creatine kinase-MB values were similar in the two groups, cardiac troponin-I levels were significantly lower in the off-pump group (8 hours, p < 0.005; 24 hours, p < 0.02, respectively). Moreover, cardiac troponin-I values 24 hours after operation correlated strongly with IL-8 levels (r = 0.61, p < 0.005), indicating that the degree of myocardial injury may be related to IL-8 production. CONCLUSIONS Compared with conventional coronary artery bypass grafting, coronary revascularization without cardiopulmonary bypass is associated with reduced cytokine responses and less myocardial injury.

Thoracoscopic Talc Insufflation Versus Talc Slurry for Symptomatic Malignant Pleural Effusion

BACKGROUND Talc has been generally accepted to be the most effective sclerosant for chemical pleurodesis, although the optimal route of administration remains unclear. METHODS We designed a prospective, randomized study to compare video-assisted thoracoscopic talc insufflation with bedside talc slurry in the treatment of malignant pleural effusion. From September 1993 to November 1995, 57 patients were recruited and randomized to either video-assisted thoracoscopic talc insufflation under general anesthesia (n = 28) or talc slurry by the bedside (n = 29). Patients with poor general condition (Karnofsky score less than 30%), poor pulmonary function (forced expiratory volume in 1 second less than 0.5 L), or trapped lungs were excluded from this study. Five grams of purified talc was used for either video-assisted thoracoscopic talc insufflation or talc slurry. RESULTS There was no statistically significant difference between the two groups of patients with respect to age, sex ratio, chest drainage duration, postprocedural hospital stay, parenteral narcotics requirement, complications, or procedure failure (ie, recurrence). CONCLUSIONS Video-assisted thoracoscopic talc insufflation has not been shown to be a superior approach compared with talc slurry in our study. Because the former demands more resources, we advocate that talc slurry should be considered as the procedure of choice in the treatment of symptomatic malignant pleural effusion in patients who do not have trapped lungs.

Thoracotomy Is Associated With Significantly More Profound Suppression in Lymphocytes and Natural Killer Cells Than Video-Assisted Thoracic Surgery Following Major Lung Resections for Cancer

Major surgery is immunosuppressive, and this could have an impact on postoperative tumor immunosurveillance and, therefore, long-term survival in cancer patients. Video-assisted thoracic surgery (VATS) lung resection is a new alternative surgical approach to thoracotomy for patients with early lung cancer. This is a pilot study to examine the postoperative changes in leukocytes, lymphocyte subsets, B cells, T cells, and natural killer (NK) cells in non-small-cell lung cancer (NSCLC) patients undergoing lung resection with VATS versus thoracotomy approaches. Twenty-one consecutive patients with resectable primary NSCLC were assigned to VATS or thoracotomy approach over a 3-month period. Blood samples were collected preoperatively and at postoperative days (POD) 1, 3, and 7 for flow cytometry determination of total leucocytes, B cells, NK cells, lymphocytes, total T cells, and T4 and T8 cell numbers. There were no demographic differences between the two groups. Compared with the preoperative values, significantly increased total white cell numbers were detected at POD 1, 3, and 7 in all patients. At POD 1, although T8 cells and NK cells were reduced in both groups, total T cell, T4 cell, and lymphocyte numbers were significantly reduced only in the thoracotomy group. At POD 7, NK cell numbers were significantly lower in the thoracotomy group than that in the VATS group. No significant intra- or intergroup differences were seen with B cells. No significant differences in survival or disease-free survival were found between the two groups. Thus, VATS major lung resection for NSCLC is associated with less, as well as quicker recovery from, postoperative immunosuppression compared with the thoracotomy approach. The clinical relevance of better preserved cellular immunity in the early postoperative period warrants confirmation from large randomized trials.

Multidisciplinary Management of Life-Threatening Massive Hemoptysis: A 10-Year Experience

BACKGROUND Life-threatening massive hemoptysis requires prompt action and thoracic surgical input. Although there are a number of reports regarding each therapeutic modality for medical or surgical treatment, the significance of a multidisciplinary strategy remains undetermined. METHODS From January 1995 to December 2005, 120 patients were referred to our cardiothoracic center with massive hemoptysis. We retrospectively reviewed and compared the outcomes of a recent 5-year period (2000 to 2005) with those from the previous 5 years (1995 to 1999), as we made major changes in our practice in 2000. We currently try to avoid surgery within 48 hours after onset of active hemoptysis and adopt bronchial artery embolization as a first-line therapy. Treatment decisions are made after discussions among intensive care unit physicians, thoracic surgeons, and interventional radiologists. RESULTS The former group had 49 patients (57.9 +/- 14.1 years old, 41 males), and the recent group, 71 (62.2 +/- 23.5 years old, 52 males). There were no significant differences for any characteristics studied between the groups. In analyses of short-term complications after surgery, the former had a higher in-hospital mortality rate than the recent group (15% versus 0%). Furthermore, postoperative complications were seen in 8 patients (30%) in the former, whereas those occurred in 3 patients (18%) in the recent group. CONCLUSION Bronchial artery embolization is an effective therapeutic tool and plays a pivotal role in management of life-threatening massive hemoptysis. Surgery is indicated when bronchial artery embolization is not suitable and can be safely performed in combination with a rigid bronchoscopy or bronchial artery embolization procedure. Our results indicate that a multidisciplinary approach should be adopted for management of life-threatening massive hemoptysis.

Video-assisted thoracic surgery lobectomy for pulmonary sequestration

Pulmonary sequestration is a rare developmental abnormality, and the patients usually present with recurrent pneumonia. We report a case of video-assisted thoracic surgery lobectomy in a 32-year-old woman with an intrapulmonary sequestration in the left lower lobe.

Video-Assisted Thoracic Surgery Thymectomy: The Better Approach

Minimally invasive video-assisted thoracic surgery (VATS) thymectomy has evolved significantly over the last decade. The most common indication for VATS thymectomy is the treatment of myasthenia gravis (MG). Video-assisted thoracic surgery thymectomy results in less postoperative pain, better preserved pulmonary function, and improved cosmesis, which can be particularly important to many young female MG patients. Results of VATS thymectomy, in terms of complete stable remission from MG and symptomatic improvement, as well as safety, are comparable with conventional surgical techniques. This more patient-friendly approach would lead to wider acceptance by MG patients and their neurologists for earlier thymectomies and improved outcomes.

Sustained increases of plasma homocysteine, copper, and serum ceruloplasmin after coronary artery bypass grafting

BACKGROUND Homocysteine (Hcy) is an independent risk factor for coronary artery disease, but there are no reports on Hcy levels in patients undergoing coronary artery bypass graft (CABG) surgery. Interactions between Hcy and copper may mediate the vasculopathic impact of Hcy, and this may play a role in vein graft failure. The aim of this study was to assess the perioperative levels of Hcy, copper, ceruloplasmin (CP), folate, and vitamin B12 in patients undergoing myocardial revascularization surgery. METHODS Blood samples were taken from 55 consecutive patients undergoing elective conventional CABG (43 male; mean age, 63.2 +/- 5.2 years) 1 day preoperatively and postoperatively at 1 day, 6 days, and 6 weeks. Hcy, copper, CP, red cell folate, vitamin B12, creatinine, and C-reactive protein (CRP) were then measured using standard clinical chemistry methods. The same protocol was applied to 10 patients (7 male; mean age, 63.3 +/- 5.2 years) undergoing off-pump coronary artery bypass (OPCAB) surgery. RESULTS In the conventional CABG group, there were significant increases in the plasma concentrations at 6 days and 6 weeks postoperatively of Hcy (from 10.1 to 11.6 and 13.5 micromol/L, respectively), plasma copper (from 13.5 to 20.3 and 18.5 micromol/L), and serum ceruloplasmin (from 0.3 to 0.41 and 0.44 g/L). CRP and vitamin B12 were elevated at 6 days but not 6 weeks after the operation. In contrast, red cell folate and creatinine were not significantly changed. The subgroup analysis for the OPCAB patients showed the same trend as for the conventional group. CONCLUSIONS Coronary surgery precipitates a significant and sustained increase in the blood concentrations of Hcy and copper, which is not due to a decrease in folate and vitamin B12, altered renal function, or inflammation. Further studies are required to establish whether the concomitant increase in Hcy and copper plays an etiological role in vein graft disease.

Thromboxane A2 receptor α promotes tumor growth through an autoregulatory feedback pathway

Tobacco smoking can cause a number of cancers. The role of thromboxane synthase (TxAS) in smoking-related cancers is largely unknown. In this study, 37 pairs of tumor and non-tumor lung tissues of non-small-cell lung cancer, 5 lung cancer cell lines, and a mouse tumor model were used to study TxAS and its related molecules. A mouse model of smoking carcinogen 4-methylnitrosamino-1-3-pyridyl-1-butanone (NNK)-induced lung tumor showed an increase in TxAS. Thromboxane A2 receptor (TP) was aberrant in lung cancer tissues of smokers. TxAS and TP were increased in lung tissues of NNK-treated mice. The in vitro studies showed that TPα rather than TPβ promoted tumor growth, and NNK increased TPα. NNK-induced TxAS, which depended on activation of cyclooxygenase-2 (COX-2), ERK and NF-κB, could be inhibited by miR-34b/c. TPα played a positive role in NNK-induced COX-2/ERK/NF-κB activation, leading to the upregulation of TxAS expression and thromboxane A2 (TxA2) synthesis. The newly synthesized TxA2 could further activate TPα, forming an autoregulatory feedback loop for TPα activation. Collectively, NNK promotes lung tumor growth via inducing TxAS and TPα, which constitutes an auto-positive feedback loop to exaggerate the growth. This study suggests that TPα and TxAS are the ideal targets against smoking-related lung cancer.

Pioglitazone Prevents Smoking Carcinogen-Induced Lung Tumor Development in Mice

Pioglitazone (PGZ), a synthetic peroxisome proliferator-activated receptor gamma (PPARγ) ligand, is known to have anti-tumor activity by inducing tumor cell apoptosis. However, it is unknown whether it can be used to prevent smoking carcinogen-induced lung tumor development. We induced mouse lung tumors using smoking carcinogen 4- methylnitrosamino-l-3-pyridyl-butanone (NNK). PGZ was given at two early stages before the tumor formation. The role and the functional mechanism of PGZ were investigated in the development of mouse pulmonary tumors. The tumor development was monitored and PPARγ activity and endogenous PPARγ ligands 15(S)-HETE, 13(S)-HODE were determined. The application of PGZ before alveolar hyperplasia formation (Group NPa) and at the early phase of alveolar hyperplasia formation (Group NPb) significantly prevented the lung tumor development especially in Group NPb mice (all p < 0.05). PGZ not only prevented the NNK-mediated reduction of endogenous ligands 15(S)-HETE and 13(S)-HODE, but also increased 13(S)-HODE level in Group NPb mice. PPARγ transcriptional activity was increased in NNKstimulated lung tissues when PGZ was given. The in vivo results were confirmed in the human lung cancer cells, which showed that PGZ induced lung cancer cell apoptosis through up-regulating nuclear PPARγ expression, inducing PPARγ transcriptional activity and increasing the levels of PPARγ ligands in NNK-treated cells. The early application of PGZ is able to prevent NNK-induced lung tumor development through maintaining the level of endogenous PPARγ ligands 15(S)-HETE and 13(S)-HODE and activation of PPARγ.

Post‐pneumonectomy empyema: Current management strategies

Post‐pneumonectomy empyema is an uncommon but potentially life‐threatening complication. It has a strong association with bronchopleural fistula, which acts as a continued source of infection into the thoracic cavity. Numerous risk factors have been identified and strategies formulated to minimize its occurrence. When bronchopleural fistula occurs, its treatment depends on several factors including extent of dehiscence, degree of pleural contamination and general condition of the patient. Early diagnosis and assessment with appropriate investigations, and aggressive therapeutic strategies are paramount in controlling sepsis, facilitating closure of fistula, and sterilization of the closed pleural space. Recent success with repeat debridement has made routine space obliteration not mandatory in management. The development of minimal‐access interventions including video‐assisted thoracic surgery, endoscopic application of tissue glue and stenting may be additional tools to complement conventional surgery in post‐pneumonectomy empyema management.