Marijuana smoke induces severe pulmonary hyperresponsiveness, inflammation, and emphysema in a predictive mouse model not via CB1 receptor activation.

Sporadic clinical reports suggested that marijuana smoking induces spontaneous pneumothorax, but no animal models were available to validate these observations and to study the underlying mechanisms. Therefore, we performed a systematic study in CD1 mice as a predictive animal model and assessed the pathophysiological alterations in response to 4-mo-long whole body marijuana smoke with integrative methodologies in comparison with tobacco smoke. Bronchial responsiveness was measured with unrestrained whole body plethysmography, cell profile in the bronchoalveolar lavage fluid with flow cytometry, myeloperoxidase activity with spectrophotometry, inflammatory cytokines with ELISA, and histopathological alterations with light microscopy. Daily marijuana inhalation evoked severe bronchial hyperreactivity after a week. Characteristic perivascular/peribronchial edema, atelectasis, apical emphysema, and neutrophil and macrophage infiltration developed after 1 mo of marijuana smoking; lymphocyte accumulation after 2 mo; macrophage-like giant cells, irregular or destroyed bronchial mucosa, goblet cell hyperplasia after 3 mo; and severe atelectasis, emphysema, obstructed or damaged bronchioles, and endothelial proliferation at 4 mo. Myeloperoxidase activity, inflammatory cell, and cytokine profile correlated with these changes. Airway hyperresponsiveness and inflammation were not altered in mice lacking the CB1 cannabinoid receptor. In comparison, tobacco smoke induced hyperresponsiveness after 2 mo and significantly later caused inflammatory cell infiltration/activation with only mild emphysema. We provide the first systematic and comparative experimental evidence that marijuana causes severe airway hyperresponsiveness, inflammation, tissue destruction, and emphysema, which are not mediated by the CB1 receptor.

Increased Wnt5a in squamous cell lung carcinoma inhibits endothelial cell motility.

BACKGROUND: Angiogenesis 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. METHODS: PPARgamma, 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. RESULTS: PPARgamma 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. CONCLUSION: During 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.

BACKGROUND: This 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). METHODS: Data 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. RESULTS: The 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). CONCLUSIONS: A 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.

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.

Multimodality treatment resulting in long-term survival in hepatocellular carcinoma.

The early detection and complex therapy of the hepatocellular carcinoma (HCC) is one of the most seasonable questions of the gastroenterology-oncology, because of the increasing prevalence of the primary liver cancer. The course of the hepatocellular carcinoma is rapid, untreated patients rarely live over 5-6 months. Combination of different treatment modalities in HCC can offer the best chances for survival. If possible, a surgical resection should be the primary procedure, followed by adjuvant cytostatic treatment and chemoembolisation. The authors report three cases with HCC with extremely long survival. The long-term survival achieved by multimodality therapy, as presented in these cases, seems to justify aggressive therapeutical approaches in HCC. It has been concluded, that early detection and complex, aggressive multimodality treatment--even repeated liver resections and surgical elimination of duplex distant metastases--can result in long-term survival with a good quality of life.

Pericardioperitoneal shunt for persistent pericardial effusions: a new drainage procedure.

We report a pericardioperitoneal shunt procedure in 2 patients with persistent pericardial effusions in which the classic surgical methods of shunting were inappropriate.

Thoracoplasty in the context of current surgical practice.

Although widely employed for well over a century as a procedure for reducing the capacity of the thoracic cavity, thoracoplasty in current practice has become a rarity. A retrospective analysis of 37 patients (29 men, 8 women) who underwent the procedure under the care of one thoracic surgeon in a 16-year period provides the basis for this presentation. Ages ranged from 23 to 82 years with a mean age of 58 +/- 12.8. The mean follow-up was 8.5 years. Nineteen patients underwent the procedure for complications after lung resection for lung cancer. There were four perioperative deaths in this group (21.1%) and 6 long-term survivors (31.6%). Eighteen patients without lung cancer underwent thoracoplasty as a planned treatment or for complications. There were no perioperative deaths, two late deaths, and 16 long-term survivors (88.9%) in the group. In the entire series, the overall perioperative mortality rate was 10.8% with no major long-term morbidity. Although proper timing and proper patient selection are essential in the use of thoracoplasty as a procedure to cope with the septic complications of lung cancer resection, it is overall a safe and successful procedure that has a relatively low mortality and that leads to considerable improvement in quality of life.

Pericardial drainage using the transdiaphragmatic route: refinement of the laparoscopic technique.

Four patients with malignant pericardial fluid requiring permanent drainage are reported. A three-port video-assisted thoracoscopic surgery modification of the pericardioperitoneal shunt procedure is described, in which the Ultracision Harmonic Scalpel is used. The supraumbilically introduced camera secures direct vision for the trocars in the left and the right hypochondrium of the patient in a modified lithotomy position. Grasping the diaphragm anterolateral to the hiatus esophagei with the manipulator, we cut through the diaphragm-pericardium complex with the Harmonic Scalpel. After creation of a hole with a diameter 3 to 5 cm, the abdomen is closed without a drain. The usage of Ultracision scalpel minimizes the risk of epicardium injury previously described with the use of scissors or electrocautery. Clips are unnecessary because the Harmonic Scalpel has a sealing effect. Two figures demonstrate the port placements and the facilitated cutting with the Harmonic Scalpel. Four patients underwent surgery using the described technique. All of them suffered from ultrasound-guided tapping or drainage-resistant, lung cancer-related malignant pericardial fluid, which caused pericardial tamponade. All the procedures were successful. The technique is easy to learn and simple to perform.

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.

[Pericardial-peritoneal shunt]. / Pericardio-peritonealis shunt.

A new shunt procedure is reported for persistent pericardial effusions. Abdominal approach to pericardial sac via transphrenic window is described. The technique proved to be useful in cases when the standard pericardiopleural procedure was not the proper solution. A decision-making algorithm is suggested when one faces different types of pericardial tamponade.

A case of fibrin sealant application for closing benign trachea-esophageal fistula (TEF).

Surgical treatment of upper airway-esophageal communications are frequently lead to failure. Having previous experience of thoracic administration of Tissucol fibrin glue authors attempted the local application in a case of TEF. A young lady suffering from myasthenia gravis required longstanding artificial ventilation. Not surprisingly a TEP developed in the area of the tracheostomy. There was no room for surgical repair of the TEF. Two administrations of rapid acting form of Tissucol was needed following local astringent therapy and enzymatic debridement to achieve a complete and permanent closure of a tracheobronchial sinus in a diameter of 5 mm. In addition of meticulous technique and of general supporting therapy special attention was paid to the followings: 1/healthy wound edges 2/ local infection control 3/dry environment 4/patient building up strategy.

Continuous epidural or intercostal analgesia following thoracotomy: a prospective randomized double-blind clinical trial.

BACKGROUND: Pain following thoracotomy is frequently associated with clinically important abnormalities of pulmonary function. The aim of the current study was to compare the efficacy of continuous thoracic epidural analgesia (EDA) to continuous intercostal (IC) block for postoperative pain and pulmonary function in a prospective, randomized, double-blinded clinical trial. METHODS: Fifty patients undergoing lung lobectomy for malignancies were randomized into two groups (25/group). Respiratory function (forced vital capacity, forced expiratory volume per 1 s/forced vital capacity, maximum midexpiratory flow rate, peak expiratory flow rate) were evaluated preoperatively, within 4 h after the operation and on the first postoperative day. Visual analog scale (VAS: 0-10) scores were evaluated four-hourly for 20 h. RESULTS: The VAS scores were significantly lower in the EDA versus IC group at the 4th, 8th, and 12th h of observation (mean +/- SD) 5.5 +/- 2.9 vs. 7.3 +/- 2.2 P = 0.04; 4.1 +/- 2.1 vs. 5.1 +/- 2.9 P = 0.02; 3.6 +/- 1.9 vs. 5.2 +/- 2.4 P = 0.01, respectively. Respiratory function parameters deteriorated significantly in both groups (P < 0.001) with no significant difference between the groups. Only one major adverse effect was detected: one patient suffered from rib osteomyelitis after intercostal cannulation and healed following surgical repair. CONCLUSIONS: The results of the present study show that following thoracotomy in the early postoperative period continuous EDA is a better pain relieving method than continuous IC block, as indicated by the VAS scores.

Palliative treatment of malignant pleural effusions by video-assisted thoracoscopic surgery.

Malignant pleural effusion (MPE) are associated with significant morbidity. Prompt clinical evaluation followed by aggressive treatment often results in successful palliation. Video-assisted Thoracic Surgery (VATS) today can be employed in the diagnosis and treatment of idiopatic and known MPE. Between January 1994 and December 1998 233 MPE patients were treated with pleurodesis. 206 of them underwent tube thoracostomy and drainage alone followed by chemical pleurodesis. In 27 out of the 233 cases VATS management was applied. These patients had undiagnosed pleural effusions or recurrent MPE following failed previous drainage and pleurodesis. The cause of the effusion was breast cancer in 11 patients, lung cancer in 9, urogenital cancer in 3, mesothelioma in 2 and other in 2. VATS intervention was thoracoscopic exploration with biopsy and directed chemical sclerosis in undiagnosed MPE (19/27) and lysis of pleural adhesions with partial decortication and pleurodesis in recurrent effusions (8/27). VATS managements were successful 26/27 after mean follow up of 6 months. Had not mortality postoperatively and severe morbidity. Chest tubes were removed 1.5 +/- 0.5 days postoperatively and hospital stay were averaged 4 +/- 1 days. We concluded that VATS is a safety and effective way of managing selected patients with pleural effusions.

Two cases of benign tracheo-gastric fistula following esophagectomy for cancer.

Two successfully managed cases of esophageal replacement for cancer complicated by neoesophagotracheal fistula are described. In both cases radical esophagectomy with a gastric pull-up was performed. In the postoperative period different complications necessitated prolonged ventilatory support and tracheostomy. In both cases a tracheo-gastric fistula developed probably because of the ischaemic effort of the tracheostomy tube and the nasogastric tube. At single stage repairs, the fistulae were divided and the gastric defects were closed directly. In the first case resection of four strictured tracheal rings and tracheal anastomosis had to be performed. In the second case the fistula was recognized earlier and stricture did not develop. The defect on the membranous trachea was patched with autologous fascia lata graft. A left pectoralis major muscle flap was interposed between the trachea and the pulled up stomach in both cases to prevent recurrence of the fistula. Treatment of this potentially life-threatening and rare condition yielded excellent results.

Predictive value of MRI in lung cancer.

Pathologic results of 543 lymph nodes removed during 164 radical surgery for lung cancer is compared with the expected findings based on preoperative MRI imaging. Specificity of T2 weighted MRI images were 95.5% for individual lymph nodes and 88.1% for TNM staging, respectively. Sensitivity was found to be 89.4% for lymph nodes and 94.6% for TNM staging of the patient. The accuracy of the MRI imaging was 84.7%. Properly chose MRI imaging and interpretation sounds to be no inferior to more invasive methods as collar mediastinoscopy, Chamberlain procedure or VATS exploration.