Thomas Chang-Yao Tsao

Elastance of the Pleural Space: A Predictor for the Outcome of Pleurodesis in Patients with Malignant Pleural Effusion

Pleural effusion is a frequent complication in patients with advanced stages of cancer [1-8], and malignant pleural effusion that is resistant to chemotherapy carries a grave prognosis [1-7]. Respiratory symptoms in patients with this disorder usually require palliative management of the effusion. Drainage of the effusion using a chest tube or during thoracoscopy with the introduction of sclerosing agents into the pleural space for pleurodesis is the most cost-effective approach [2-8]. Pleurodesis is unsuccessful in patients with symptomatic malignant pleural effusion and trapped lung (defined as poor approximation of the pleurae after drainage of the effusion); insertion of a thoracostomy tube or performance of thoracoscopy in such patients provides little benefit [2-57, 9, 10]. Thus, the diagnosis of trapped lung before such invasive procedures is important but difficult [5, 6]. The outcome of pleurodesis in patients who have malignant pleural effusion without trapped lung, however, is difficult to predict. Therefore, we studied pleural elastance as a predictor of successful pleurodesis and compared its predictive ability with that of the biochemical characteristics of pleural fluid. Methods Patients Patients who were admitted to our institution because of symptomatic malignant pleural effusion and who required therapeutic thoracentesis were candidates for this 3-year prospective study. Malignant effusion was diagnosed only if malignant cells were found in a pleural biopsy specimen or effusion fluid. Exclusion criteria were 1) previous effusion of chemotherapy-sensitive cell types [for breast cancer, ovarian cancer, small-cell cancer of the lung, or lymphoma, for example], except when the patients had undergone a course of chemotherapy that had not eliminated the effusion; 2) chemotherapy or radiotherapy previously administered or planned within 2 months; 3) life expectancy of 1 month or less; and 4) loculated pleural effusion. Measurements and Interventions Figure 1 is a diagram of the device that was used to measure the elastance of the pleural space. Measurements were done while patients were in a sitting position. Under ultrasonographic guidance, an appropriate intercostal space was selected. After a local anesthetic was administered, 20 mL of pleural effusion was drawn into a heparin-rinsed plastic syringe for the measurement of glucose level and pH and for cytologic examination. Then, a 16-gauge intracatheter needle was inserted into the pleural space. The needle was attached to a three-way stopcock with two extension tubes that led to a central venous pressure monitor and a 50-mL syringe. The whole system was filled with normal, heparinized saline. Using a leveling rod, we marked a zero point on the central venous pressure monitor at the level of the puncture site. The pleural pressure, defined as the mean of the pleural fluid pressures during inspiration and expiration, was measured immediately and after each 100 mL of effusion was withdrawn. Thoracentesis was terminated when the pressure was lower than 10 cm H2O, when the patient developed symptoms potentially related to reexpansion pulmonary edema, or when a total of 500 mL of effusion had been drained. The elastance of the pleural space was calculated as the change in pressure of the pleural effusion (in cm H2O) divided by the amount of fluid removed [11]; the standard measure was expressed as being equivalent to the decline in pressure of the pleural effusion after 500 mL of fluid had been removed. In five patients who had a decrease in pressure of at least 19 cm H2O and trapped lung, thoracentesis was stopped before 500 mL of effusion had been drained; the elastance value in these patients was adjusted by linear extrapolation on the basis of the change in pressure that would have occurred if 500 mL had actually been removed [11]. Figure 1. Device used to measure the elastance of the pleural space. After these measurements had been done, a 9.3-mm thoracostomy tube connected to a watersealed bottle was placed in the pleural space for further drainage of the effusion by gravity. Suction was applied to the chest tube only if the patient had radiographic evidence of trapped lung. Radiography was done to ensure proper positioning of the thoracostomy tube. Drainage was discontinued when less than 150 mL of effusion was drained per day [3, 7, 12] for 2 consecutive days and the lung had reexpanded, when less than 250 mL of effusion was drained per day for 4 consecutive days and the lung had reexpanded, or when drainage had continued for 10 days. When one of the three criteria was met, radiography was done to evaluate the reexpansion of the affected lung and the approximation of the pleurae. Figure 2 shows the degrees of reexpansion of the affected lung and the approximation of the pleurae. In category 1, the lung had completely reexpanded and the pleurae had approximated well. In category 2, the affected lung had reexpanded and the pleurae had approximated in most areas, but a small amount of residual pneumothorax, pleural effusion, or some heterogeneous white patches were evident on radiographs. In category 3, the lung did not reexpand and the visceral and parietal pleurae were separated by pneumothorax in most places. The radiographs were evaluated by at least two of the authors. If reexpansion of the lung and approximation of the pleurae were difficult to interpret, the patients were placed in category 2. Patients in category 1 or 2 were classified as having a nontrapped lung. Figure 2. Categories of reexpansion of the affected lung and approximation of the pleurae. The chest tube was then clamped, and we injected 60 mg of bleomycin diluted in 100 mL of normal saline (usual-dose group) [4, 5, 7, 8, 13-15] or, in the latter half of the study, 30 mg diluted in 50 mL of normal saline (low-dose group) [13, 14] into the pleural space for pleurodesis in all patients except two who had trapped lung. The body position of the patient was changed if the patient was not too ill [16-18]. The chest tube was reopened 2 hours later and removed the next day [5]. Chest radiography was done to ensure that the chest tube had been removed properly. Patients were then followed closely in the outpatient clinic, and chest radiography was done to evaluate the outcome of pleurodesis. If the results were equivocal, we did either chest ultrasonography with or without diagnostic thoracentesis or computed tomography of the chest. The results of pleurodesis were evaluated 30 days after the chest tube was removed and then until the patient died or was lost to follow-up [3, 4, 12-15, 19]. Successful pleurodesis was defined as no recurrence of effusion, recurrence of only a small amount of effusion, or loculated effusion and elimination of the requirement for further therapeutic thoracentesis to alleviate symptoms [10, 12-15, 19]. Unsuccessful pleurodesis was defined as recurrence of the effusion in an amount similar to that seen before treatment or the requirement for further therapeutic thoracentesis to alleviate symptoms. Statistical Analysis The two-sample t-test was used to compare the mean elastance, pH, glucose level, and duration of follow-up for patients with trapped and nontrapped lungs. The Fisher exact test was used to evaluate the association between categorized variables. Confidence intervals for means and proportions were determined when appropriate. Results Sixty-five patients (38 men and 27 women) between 39 and 83 years of age (mean age, 62.7 years) were included in the study. Two patients had gastric cancer, 2 had breast cancer, 1 had renal cancer, 1 had rectal cancer, 45 had bronchogenic adenocarcinoma, and 14 had adenocarcinoma of uncertain origin. All patients had pleural effusion on chest radiography that reached the hilar level or higher in the sitting or standing position. Fourteen patients had trapped lung, and 51 did not have trapped lung. As Table 1 and Figure 3 show, 11 of 14 patients with trapped lung (groups 1 and 4) had an elastance of 19 cm H2O or more, although only 3 of the 51 patients without trapped lung (groups 2, 3, and 5) had such an elastance (P < 0.001). Mean elastance was 30.59 cm H2O in the 14 patients with trapped lung and 8.31 cm H2O in the 51 patients without trapped lung (difference, 22.3 cm H2O [95% CI, 11.1 to 33.5]; P = 0.001). Table 1. Results of Chest-Tube Drainage and Pleurodesis at 1 Month Figure 3. Relation of pleural elastance, effusion pH, effusion glucose level, trapped lung, and outcome of pleurodesis. Five patients who had trapped lung were lost to follow-up at 1 month (Figure 3; group 1); pleurodesis was noted to have been unsuccessful in two of these five patients before they were lost to follow-up. Another five patients with elastance less than 19 cm H2O who did not have trapped lung (Figure 3; group 2) were also not evaluated at 1 month because of loss to follow-up (n = 3), death (n = 1), or postoperative cardiac tamponade (n = 1). Tight pleural approximation was noted during surgery in the patient with postoperative cardiac tamponade. Fifty-five patients were evaluated 1 month after the thoracostomy tube was removed (Figure 3; groups 3, 4, and 5). Pleurodesis was unsuccessful in all 9 patients who had trapped lung (Figure 3; group 4) and in the 3 patients who had an elastance of 19 cm H2O or more without trapped lung (Figure 3; group 5). In contrast, 42 of the 43 patients (98%) with an elastance less than 19 cm H2O without trapped lung had successful pleurodesis (Figure 3; groups 3 and 5). The 14 patients with trapped lung had a higher elastance (30.59 cm H2O) than did the 51 patients without trapped lung (8.31 cm H2O) (P = 0.001); the effusion from the former group also had a lower pH (7.133 compared with 7.308; P = 0.001) and a lower glucose level (3.16 mmol/L compared with 5.27 mmol/L; P = 0.011) than the effusion from the latter group. Duration of follow-up in the group with trapped lung (2.7 months) was similar t

EGCG inhibits transforming growth factor-β-mediated epithelial-to-mesenchymal transition via the inhibition of Smad2 and Erk1/2 signaling pathways in nonsmall cell lung cancer cells.

Transforming growth factor-β (TGF-β)-mediated epithelial mesenchymal transition (EMT) of human lung cancer cells may contribute to lung cancer metastasis. It has been reported that EGCG can inhibit tumorigenesis and cancer cell growth in lung cancer; however, the effect of EGCG on EMT in nonsmall cell lung cancer (NSCLC) cells has not been investigated. In this study, we found that NSCLC cells A549 and H1299 were converted to the fibroblastic phenotype in response to TGF-β. Epithelial marker E-cadherin was down-regulated, and mesenchymal marker vimentin was up-regulated simultaneously. Our results illustrated that TGF-β was able to induce EMT in NSCLC cells, and EGCG would reverse TGF-β-induced morphological changes, up-regulate the expression of E-cadherin, and down-regulate the expression of vimentin. Immunofluorescent staining also demonstrated that E-cadherin was up-regulated and that vimentin was down-regulated by EGCG pretreatment. Moreover, wound-healing and the in vitro invasion assay showed that EGCG could inhibit TGF-β-induced migration and invasion of NSCLC cells. By using the dual-luciferase reporter assay, we demonstrated that EGCG inhibited TGF-β-induced EMT at the transcriptional level. EGCG decreased the phosphorylation of Smad2 and Erk1/2, inhibited the nuclear translocation of Smad2, and repressed the expression of transcription factors ZEB1, Snail, Slug, and Twist, and up-regulated the expression of E-cadherin. In summary, our results suggest that EGCG can inhibit TGF-β-induced EMT via down-regulation of phosphorylated Smad2 and Erk1/2 in NSCLC cells.

Carbofuran-Induced Delayed Neuropathy

Background: Although carbamates have been widely used in the world for many years, carbamate-induced delayed neuropathy is rare. We report what appears to be delayed neuropathy caused by poisoning with carbofuran, a cholinesterase-inhibiting carbamate, although the certainty of diagnosis is somewhat limited by the lack of a sural nerve biopsy and spinal fluid examination. Case Report: A 23-year-old man attempted suicide by ingesting 100 mL of carbofuran (2,3-dihydro-2,2-dimethyl-7-benzofuranyl methylcarbamate). After recovering from acute cholinergic toxicity, he had notable paresthesia in his lower limbs and difficulty walking. Electrophysiologic findings revealed sensorimotor neuropathy. Recovery began at 1 week and continued for 4 months. A similar delayed neuropathy has been described with carbamate, 1-naphthyl N-methylcarbamate, and m-tolyl methylcarbamate, but not with carbofuran insecticides.

Hypokalemic Muscular Paralysis Causing Acute Respiratory Failure Due to Rhabdomyolysis with Renal Tubular Acidosis in a Chronic Glue Sniffer

Case Report: A 34-year-old male was admitted to the emergency department with the development of quadriparesis and respiratory failure due to hypokalemia after prolonged glue sniffing. The patient was subsequently given mechanical ventilatory support for respiratory failure. He was weaned from the ventilator 4 days later after potassium replacement. Toluene is an aromatic hydrocarbon found in glues, cements, and solvents. It is known to be toxic to the nervous system, hematopoietic system, and causes acid-base and electrolyte disorders. Acute respiratory failure with hypokalemia and rhabdomyolysis with acute renal failure should be considered as potential events in a protracted glue sniffing.

Video‐assisted thoracic surgery for spontaneous haemopneumothorax

Background and objective:  The aim of this study was to review the treatment options for spontaneous haemopneumothorax (SHP) by video‐assisted thoracoscopic surgery (VATS).

Effects of inverse ratio ventilation versus positive end-expiratory pressure on gas exchange and gastric intramucosal PCO2 and pH under constant mean airway pressure in acute respiratory distress syndrome

Background In patients with acute respiratory distress syndrome, whether inverse ratio ventilation differs from high positive end-expiratory pressure (PEEP) for gas exchange under a similar mean airway pressure has not been adequately examined. The authors used arterial oxygenation, gastric intramucosal partial pressure of carbon dioxide (Pico2), and pH (pHi) to assess whether pressure-controlled inverse ratio ventilation (PC-IRV) offers more benefits than pressure-controlled ventilation (PCV) with PEEP. Methods Seventeen acute respiratory distress syndrome patients were enrolled and underwent mechanical ventilation with a PCV inspiratory-to-expiratory ratio of 1:2, followed by PC-IRV 1:1 initially. Then, they were randomly assigned to receive PC-IRV 2:1, then 4:1 or 4:1, and then 2:1, alternately. The baseline setting of PCV 1:2 was repeated between the settings of PC-IRV 2:1 and 4:1. Mean airway pressure and tidal volume were kept constant by adjusting the levels of peak inspiratory pressure and applied PEEP. In each ventilatory mode, hemodynamics, pulmonary mechanics, arterial and mixed venous blood gas analysis, Pico2, and pHi were measured after a 1-h period of stabilization. Results With a constant mean airway pressure, PC-IRV 2:1 and 4:1 decreased arterial and mixed venous oxygenation as compared with baseline PCV 1:2. Neither the global oxygenation indices with oxygen delivery and uptake nor Pico2 and pHi were improved by PC-IRV. During PC-IRV, applied PEEP was lower, and auto-PEEP was higher. Conclusion When substituting inverse ratio ventilation for applied PEEP to keep mean airway pressure constant, PC-IRV does not contribute more to better gas exchange and gastric intramucosal Pico2 and pHi than does PCV 1:2 for acute respiratory distress syndrome patients, regardless of the inspiratory-to-expiratory ratios.

Does empirical treatment of community-acquired pneumonia with fluoroquinolones delay tuberculosis treatment and result in fluoroquinolone resistance in Mycobacterium tuberculosis? Controversies and solutions.

Abstract The role of fluoroquinolones (FQs) as empirical therapy for community-acquired pneumonia (CAP) remains controversial in countries with high tuberculosis (TB) endemicity owing to the possibility of delayed TB diagnosis and treatment and the emergence of FQ resistance in Mycobacterium tuberculosis. Although the rates of macrolide-resistant Streptococcus pneumoniae and amoxicillin/clavulanic acid-resistant Haemophilus influenzae have risen to alarming levels, the rates of respiratory FQ (RFQ) resistance amongst these isolates remain relatively low. It is reported that ca. 1–7% of CAP cases are re-diagnosed as pulmonary TB in Asian countries. A longer duration (≥7 days) of symptoms, a history of night sweats, lack of fever (>38°C), infection involving the upper lobe, presence of cavitary infiltrates, opacity in the lower lung without the presence of air, low total white blood cell count and the presence of lymphopenia are predictive of pulmonary TB. Amongst patients with CAP who reside in TB-endemic countries who are suspected of having TB, imaging studies as well as aggressive microbiological investigations need to be performed early on. Previous exposure to a FQ for >10 days in patients with TB is associated with the emergence of FQ-resistant M. tuberculosis isolates. However, rates of M. tuberculosis isolates with FQ resistance are significantly higher amongst multidrug-resistant M. tuberculosis isolates than amongst susceptible isolates. Consequently, in Taiwan and also in other countries with TB endemicity, a short-course (5-day) regimen of a RFQ is still recommended for empirical therapy for CAP patients if the patient is at low risk for TB.

Effects of thermal preconditioning on the ischemia-reperfusion-induced acute lung injury in minipigs.

ABSTRACT Lung ischemia-reperfusion (I/R) injury plays an important role in many clinical issues. A series of mechanisms after I/R has been uncovered after numerous related studies. Organ preconditioning (PC) is a process whereby a brief antecedent event, such as transient ischemia, oxidative stress, temperature change, or drug administration, bestows on an organ an early or delayed tolerance to further insults by the same or different stressors. In this study, we want to uncover the optimal thermal PC patterns that cause maximal early or delayed protective effect on the subsequent pulmonary I/R with the use of miniature pig model. Twenty-eight 15- to 20-kg weight Lanyu miniature pigs are used and divided into four groups (seven sham operation control [NC], seven PC only [PC], seven I/R [I/R], and seven PC followed by I/R [PC + I/R]). The PC was performed with the animals being anesthetized and, using an alternative hyperthermic (40°C) and normothermic moist air to ventilate their lungs for 15 min, respectively, for 2 cycles, followed by I/R, which consists of 90 min of blocking the perfusion and ventilation of the left lung followed by 240 min of reperfusion. Control animals had a thoracotomy with hilar dissection only. Indicators of lung injury included hemodynamic parameters, blood gas analysis, histopathological (lung pathology, wet/dry weight ratio, myeloperoxidase assay), and molecular biological profiles (interleukin-1β [IL-1β], IL-6, tumor necrosis factor-α by enzyme-linked immunosorbent assay analysis). Lung tissue heat shock protein 70 (HSP-70) expression was also detected by Western blotting. This model of lung I/R induced significant lung injury with pulmonary hypertension, increased pulmonary vascular resistance, and pulmonary venous hypoxemia at the ischemia side, increased pulmonary tissue injury score and neutrophil infiltration, increased wet/dry ratio, myeloperoxidase assay, tumor necrosis factor-α, IL-1β, and IL-6 assay. This type of thermal PC would not injure the lung parenchyma or tracheal epithelium. Moreover, it could attenuate the I/R-related lung injury, with some of these parameters improved significantly. Increased expression of HSP-70 was also found in the group of PC plus I/R than the I/R only. Less prominent and transient increase in expression of HSP-70 was found in the PC group. We concluded that the intratracheal thermal PC can effectively attenuate I/R-induced lung injury through various mechanisms, including the decrease of various proinflammatory cytokines. The mechanism of its protective effect might be related to the increased expression of HSP-70.Abbreviations - IL-Interleukin; I/R-ischemia-reperfusion; MPAP-mean pulmonary arterial pressure; MPO-myeloperoxidase; PC-preconditioning; TNF-tissue necrosis factor; W/D ratio-wet-to-dry weight ratio

Extramedullary plasmacytoma (EMP): Report of a case manifested as a mediastinal mass and multiple pulmonary nodules and review of literature

BackgroundExtramedullary plasmacytoma (EMP) is a rare plasma cell neoplasm of soft tissue without bone marrow involvement or other systemic characteristics of multiple myelomaCase presentationA 42 year-old woman presented with intermittent dry cough of 10 months duration. Her breathing sound was slightly coarse without rales or rhonchi on auscultation. CT scan revealed a right anterior mediastinal shadow with multiple pulmonary nodular lesions. A video-assisted thoracoscopic surgery (VATS) was performed. Histopathology showed it to be a myeloma.ConclusionThis is the first presentation of EMP with a mediastinal mass with multiple pulmonary nodules.

Increased Survivin mRNA in Malignant Pleural Effusion is Significantly Correlated with Survival

OBJECTIVE The sensitivity of cytologic examination of pleural effusions is variable and not predictive of prognosis. Survivin is an inhibitor of apoptosis that may be a novel diagnostic/prognostic marker of cancers. This study aimed to determine the diagnostic and prognostic value of measuring survivin mRNA levels in pleural effusions. METHODS Eighty-eight consecutive pleural effusion samples were examined for both cytology and survivin mRNA level. The accuracy of diagnosis and the correlation between survivin mRNA level and survival in malignant pleural effusion (MPE) were determined. Pleural effusions were divided into three groups: Group I, malignancy-associated (n = 44); Group II, inflammatory (n = 27); and Group III, transudative (n = 17). RESULTS Survivin mRNA levels in Group I (1.03 +/- 0.61, range 0-2.96) were significantly higher than those in Groups II (0.45 +/- 0.69, range 0-3.30) and III (0.08 +/- 0.22, range 0-0.71) (P < 0.001). Survivin mRNA level was significantly higher in MPE than in non-MPE. The cut-off value for survivin mRNA levels in pleural effusions was 0.074 for the diagnosis of malignancies, with sensitivity, specificity, and positive and negative predictive values of 96%, 45%, 45% and 96%, respectively. Survivin mRNA level in pleural effusions of cancer patients significantly correlated with poor survival. CONCLUSIONS Survivin mRNA level is significantly higher in MPEs. Over-expression of survivin mRNA correlates with poor prognosis in cancer patients.