Effect of lidocaine cream analgesia for chest drain tube removal after video-assisted thoracoscopic surgery for lung cancer: a randomized clinical trial.

BACKGROUND AND OBJECTIVES: Pain management makes an important contribution to good respiratory care and early recovery after thoracic surgery. Although the development of video-assisted thoracoscopic surgery (VATS) has led to improved patient outcomes, chest tube removal could be distressful experience for many patients. The aim of this trial was to test whether the addition of lidocaine cream would have a significant impact on the pain treatment during chest tube removal from patients who had undergone VATS for lung cancer. METHODS: This clinical trial was a double-blind randomized study. Forty patients with histologically confirmed lung cancer amenable to lobectomy/segmentectomy were enrolled. All patients had standard perioperative care. Patients were randomly assigned to receive either epidural anesthesia plus placebo cream (placebo, Group P) or epidural anesthesia plus 7% lidocaine cream cutaneously around the chest tube insertion site and on the skin over the tube's course 20 min (Group L) before chest drain removal. RESULTS: Visual analog scale (VAS) scores were higher in Group P (median 5, IQR, 3.25-8) than in Group L (median 2, IQR, 1-3). Pain intensities measured using a PainVision system were also higher in Group P (median 296.7, IQR, 216.9-563.5) than Group L (median 41.2, IQR, 11.8-97.0). VAS scores and the pain intensity associated with chest drain removal were significantly lower in Group L than Group P (p=0.0002 vs p<0.0001). CONCLUSION: Analgesia using lidocaine cream is a very simple way to reduce the pain of chest tube removal after VATS. TRIAL REGISTRATION NUMBER: UMIN000013824.

Phase II trial of induction chemotherapy with carboplatin and paclitaxel plus bevacizumab in patients with stage IIIA to IV nonsquamous non-small cell lung cancer.

PURPOSE: Surgery remains the best curative treatment option for non-small cell lung cancer (NSCLC), but is of benefit only to patients with localized disease. A meta-analysis showed a significant beneficial effect of induction chemotherapy on survival, but there is still no clear evidence. This phase II study was conducted to establish whether induction chemotherapy with carboplatin (CBDCA) and paclitaxel (PTX) plus bevacizumab prior to surgery reduces the risk of progression. METHODS: The subjects of this study were 29 patients with treatment-naive nonsquamous NSCLC (clinical stages IIIA to IV). Patients received PTX (200 mg/m2), CBDCA (area under the curve, 5), and bevacizumab (15 mg/kg) followed by surgery. Chemotherapy was repeated every 3 weeks for up to six cycles. RESULTS: The overall response rate was 72.4%. Of the 29 patients, ten underwent surgery after the induction chemotherapy and complete resection was achieved in 7 (70%). The median progression-free-survival (PFS) time and the 3-year PFS rate were 0.92 years and 16.2%, respectively. The median overall survival (OS) time and the 3-year OS rate were 1.96 years and 44.9%, respectively. CONCLUSION: Combined modality therapy with surgery after induction chemotherapy with CBDCA and PTX plus bevacizumab is clinically feasible and tolerable for patients with unknown or negative molecular profiles.

A case of pulmonary hamartoma showing rapid growth.

A 65-year-old man was admitted for detailed examination of a growing nodular shadow in the left lung. The nodular shadow was initially detected in a routine chest X-ray check-up in March 2012 that warranted regular chest X-ray follow-up. The nodular shadow increased in size from 12 × 15 mm to 15 × 20 mm within five months. The calculated tumor doubling time (TDT) in our case was approximately 132.2 days. A malignant tumor was strongly suspected based on the rapid growth, and tumorectomy was thus performed. Cartilaginous tissue accounted for most of the pathological specimen, but a small amount of an epithelial component was observed histologically, and we diagnosed a hamartoma. Hamartoma generally shows slow annual growth, but it is important to recognize that rapid enlargement occurs in some cases.

Resection of a giant, invasive malignant solitary fibrous tumor of pleura.

Solitary fibrous tumor of pleura (SFTP) is a rare mesenchymal neoplasm that most commonly involves the pleura, is probably derived from fibroblasts, and has no relationship to malignant mesothelioma. Here, we report a case of complete resection of a giant malignant SFTP. A 61-year-old woman developed fever and left flank pain. Computed tomography revealed the tumor to be 13 cm in size and located in the left thoracic cavity, directly invading the left lower lobe of the lung. The patient underwent radical resection and left lower lobectomy. Immunohistochemical examination revealed a dense proliferation of spindle-shaped cells with ovoid nuclei and collagen fibers hyperplasia. The cells were positive for CD34 and vimentin, and were negative for cytokeratin AE1/AE3, calretinin, S-100 and smooth muscle α-actin. SFTPs have malignant potential, as 20-30 % of resected SFTPs reportedly contain malignant components. Careful long-term clinical follow-up is therefore required for all cases of SFTP.

Postoperative bronchial stump fistula after lobectomy: response to occlusion with polyglycolic acid mesh and fibrin glue via bronchoscopy.

Bronchial stump fistula after resection of lung cancer is an extremely difficult to treat postoperative complication. Endoscopic fistula closure is a favorable alternative, potentially avoiding major surgical intervention. an 80-year-old man underwent curative resection of squamous cell carcinoma by left upper lobectomy of the lung. The patient suddenly developed massive subcutaneous emphysema on postoperative day 10. Bronchoscopy revealed a fistula about 3 mm in diameter at the lateral edge of the bronchial stump. Concentrated fibrinogen 0.5 ml (fluid A) was sprinkled on the bronchial fistula initially, and then pieces of polyglycolic acid mesh presoaked in fluid A or fluid B (thrombin) of the fibrin glue were pushed with biopsy forceps into the fistula in an alternating fashion (A→B→A→B) under endotracheal local anesthesia. Air leakage was stopped, and the patient did not develop empyema. Particularly for patients in poor general condition, our noninvasive technique seems to serve as a therapy of first choice.

Late-onset chylothorax after pulmonary resection for lung cancer.

Chylothorax is a relatively rare complication of thoracic surgery. Most instances of chylothorax after pulmonary resection are diagnosed within 3 days after surgery. Hence, late-onset chylothorax is rare. A 68-year-old woman underwent right lower lobectomy and mediastinal dissection for lung cancer. After discharge, the patient developed a dry cough, and chest radiography more than 3 months after surgery revealed a right-sided pleural effusion occupying more than half of the right hemithorax, which we diagnosed as late-onset chylothorax. Treatment comprised chest drainage, subcutaneous octreotide, and pleurodesis by injecting a preparation of OK-432. Follow-up chest radiography confirmed no reaccumulation of fluid. Three months later no recurrence of pleural effusion was detected. We report a rare case of postoperative late-onset chylothorax that proved difficult to treat.

Activation of endothelial NADPH oxidase during normoxic lung ischemia is KATP channel dependent.

Previous studies have shown endothelial cell membrane depolarization and generation of reactive oxygen species (ROS) in endothelial cells with abrupt reduction in shear stress (ischemia). This study evaluated the role of ATP-sensitive potassium (K(ATP)) channels and NADPH oxidase in the ischemic response by using Kir6.2-/- and gp91(phox)-/- mice. To evaluate ROS generation, we subjected isolated perfused mouse lungs labeled with 2',7'-dichlorodihydrofluorescein (DCF), hydroethidine (HE), or diphenyl-1-pyrenylphosphine (DPPP) to control perfusion followed by global ischemia. In wild-type C57BL/6J mice, imaging of subpleural endothelial cells showed a time-dependent increase in intensity for all three fluorescence probes with ischemia, which was blocked by preperfusion with cromakalim (a K(ATP) channel agonist) or diphenyleneiodonium (DPI, a flavoprotein inhibitor). Endothelial cell fluorescence with bis-oxonol, a membrane potential probe, increased during lung ischemia indicating cell membrane depolarization. The change in membrane potential with ischemia in lungs of gp91(phox)-/- mice was similar to wild type, but ROS generation did not occur. Lungs from Kir6.2-/- showed marked attenuation of the change in both membrane potential and ROS production. Thus membrane depolarization during lung ischemia requires the presence of a K(ATP) channel and is required for activation of NADPH oxidase and endothelial ROS generation.

Increased expression of myosin light chain kinase mRNA is related to metastasis in non-small cell lung cancer.

BACKGROUND: The invasiveness of tumor cells depends in large part on their motility, which in turn depends on cytoskeletal function. A major cytoskeletal component involved in cell motility is myosin II, the classical form of myosin first identified in muscle but also expressed in nonmuscle cells. Myosin II is activated by myosin light chain kinase (MLCK), which phosphorylates it on its regulatory light chain. In this context, the contribution made by MLCK to tumor cell motility and invasiveness has been investigated extensively in vitro, but clinical evidence of such a contribution has been lacking. In the present study, therefore, we examined the role of MLCK in the metastasis of non-small cell lung cancer (NSCLC) in a clinical setting. METHODS: We measured MLCK mRNA expression in tumor samples from 39 NSCLC patients using real-time semiquantitative reverse transcription polymerase chain reaction carried out in a LightCycler. We then correlated MLCK mRNA expression with known clinicopathological factors. RESULTS: We found that levels of MLCK mRNA expression were higher in patients who showed disease recurrence and distant metastasis than in those who did not. Moreover, the 3-year disease-free survival rate among patients showing lower levels of MLCK mRNA expression [log10(MLCK/GAPDH) <1.4] was significantly greater than among those showing higher MLCK mRNA expression [log10(MLCK/GAPDH) > or =1.4] (87.5 vs. 50.0%; log-rank test, p = 0.021). CONCLUSION: These findings are the first clinical evidence that expression of MLCK is correlated with disease recurrence and distant metastasis in NSCLC.

Membrane depolarization and NADPH oxidase activation in aortic endothelium during ischemia reflect altered mechanotransduction.

We previously showed that "ischemia" (abrupt cessation of flow) leads to rapid membrane depolarization and increased generation of reactive oxygen species (ROS) in lung microvascular endothelial cells. This response is not associated with anoxia but, rather, reflects loss of normal shear stress. This study evaluated whether a similar response occurs in aortic endothelium. Plasma membrane potential and production of ROS were determined by fluorescence microscopy and cytochrome c reduction in flow-adapted rat or mouse aorta or monolayer cultures of rat aortic endothelial cells. Within 30 s after flow cessation, endothelial cells that had been flow adapted showed plasma membrane depolarization that was inhibited by pretreatment with cromakalim, an ATP-sensitive K(+) (K(ATP)) channel agonist. Flow cessation also led to ROS generation, which was inhibited by cromakalim and the flavoprotein inhibitor diphenyleneiodonium. Aortic endothelium from mice with "knockout" of the K(ATP) channel (K(IR)6.2) showed a markedly attenuated change in membrane potential and ROS generation with flow cessation. In aortic endothelium from mice with knockout of NADPH oxidase (gp91(phox)), membrane depolarization was similar to that in wild-type mice but ROS generation was absent. Thus rat and mouse aortic endothelial cells respond to abrupt flow cessation by K(ATP) channel-mediated membrane depolarization followed by NADPH oxidase-mediated ROS generation, possibly representing a cell-signaling response to altered mechanotransduction.

Mediastinal neurofibroma originating from the left intrathoracic phrenic nerve: report of a case.

We report a case of mediastinal neurofibroma originating from the left phrenic nerve in a 42-year-old woman who was referred to us after a routine chest X-ray showed a smooth, round abnormal shadow in the left middle lung field adjacent to the heart. We resected a 25 x 20 x 20-mm tumor by video-assisted thoracic surgery. Histopathological examination confirmed that the lesion was a mediastinal neurofibroma originating from the left phrenic nerve without von Recklinghausen's disease. Neurogenic mediastinal tumors originating from the phrenic nerve are very rare, and to the best of our knowledge, no other case of a mediastinal neurofibroma originating from the phrenic nerve in a patient without von Recklinghausen's disease has ever been reported.

Expression of tissue factor mRNA and invasion of blood vessels by tumor cells in non-small cell lung cancer.

PURPOSE: Tissue factor (TF), an initiator of the extrinsic coagulation cascade, is also expressed in a wide range of cancer cells and plays an important role in cancer progression and metastasis, as well as in processes independent of the blood coagulation pathway. For example, by acting as an adhesion molecule enabling tissue invasion, TF may play a key role in the metastatic process and angiogenesis in non-small cell lung cancer (NSCLC). METHODS: To further investigate the role of TF on tumor cell invasion in NSCLC, we measured the TF mRNA expression in the tumors of 42 NSCLC patients using real-time quantitative reverse transcription - polymerase chain reaction carried out in a LightCycler. We then compared the TF mRNA expression with histological evidence of invasion of blood and lymphatic vessels by tumor cells. RESULTS: Although there was no significant relationship between the TF mRNA expression and the invasion of lymphatic vessels, the TF mRNA expression was significantly higher in tumors that invaded blood vessels (Log(10) TF mRNA/GAPDH mRNA = 2.16 +/- 0.18) than in those that did not (1.59 +/- 0.16; P = 0.03). CONCLUSION: These results suggest that TF plays a major role in blood vessel invasion by tumor cells in NSCLC.

Indication for preoperative localization of small peripheral pulmonary nodules in thoracoscopic surgery.

OBJECTIVE: Widespread clinical use of helical computed tomography has improved the detection rate for small peripheral pulmonary nodules. As a result, use of thoracoscopic surgery to confirm the diagnosis of small peripheral pulmonary nodules has become more important than ever before. However, if small peripheral pulmonary nodules are too small or located too deeply to detect thoracoscopically, it is necessary to mark the small peripheral pulmonary nodules preoperatively. The purpose of this study was to determine indications for preoperative hookwire marking in thoracoscopic resection of small peripheral pulmonary nodules. METHODS: A total of 120 patients underwent thoracoscopic pulmonary resection in our institute from 1999 to 2001. Small peripheral pulmonary nodules were marked preoperatively in 61 of these patients by means of percutaneous placement of a hookwire under computed tomographic guidance. The hookwire-marked small peripheral pulmonary nodules either were smaller than 10 mm or were located more than 10 mm below the pleural surface. RESULTS: Although 9 of the hookwire-marked small peripheral pulmonary nodules were easily identified during thoracoscopy, the other 52 small peripheral pulmonary nodules could not have been identified during thoracoscopy without the hookwire marking. Of the 59 small peripheral pulmonary nodules that were not hookwire marked, 7 required conversion to thoracotomy to locate the nodules. Small peripheral pulmonary nodules from both groups were examined and assigned to either an undetectable or detectable group. Discriminant function analysis indicated that a linear function (ie, depth = 0.836 x size - 2.811) could be used to differentiate between undetectable and detectable small peripheral pulmonary nodules, and preoperative hookwire marking for small peripheral pulmonary nodules should be considered for nodules in the region above those. CONCLUSION: The results suggest that this formula might serve as an indication for preoperative marking of small peripheral pulmonary nodules in thoracoscopic resection.

Nafamostat mesilate attenuates radical formation in the rat lung infused with endotoxin.

We previously reported direct evidence of respiratory bursting by neutrophils in the pulmonary circulation of endotoxin-infused rats. To evaluate the effect of the protease inhibitor nafamostat mesilate (NM) on leukocyte-mediated radical formation in the pulmonary circulation of rats infused with endotoxin, we observed and measured the number of sticking leukocytes and quantified radical production in the pulmonary circulation of endotoxin-infused rats by means of a fluorescent imaging technique. Plasma C3a (desArg) was also measured using an enzyme-linked immunosorbent assay. Three groups (n = 5) of rats were infused with 4.5 mg/kg/h endotoxin (Et group), 50 microg/kg/h NM + endotoxin (NM group), or physiological saline (Ct group) for 2 h. The number of the leukocytes adhering within pulmonary capillaries, oxygen radical production in the rat pulmonary circulation, and plasma C3a (desArg) were all lower in the NM group than in the Et group. The leukocytes producing oxygen radicals were confirmed to be neutrophils by electron microscopic analysis of cerium deposition. We conclude that NM attenuates plasma C3a formation, neutrophil adherence to pulmonary capillaries, and their production of oxygen radical in rats infused with endotoxin.