In epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) therapy for lung cancer patients, acquired resistance develops almost inevitably and this limits the improvement in patient ...outcomes. EGFR T790M mutation and MET amplification are the two main mechanisms underlying this resistance, but the relationship between these two mechanisms is unclear. In this study, we explored their relationship using in vitro models and autopsy specimens.
Erlotinib-resistant HCC827 (HCC827ER) cells were developed by chronic exposure to erlotinib at increasing concentrations. HCC827EPR cells were also developed by chronic exposure to erlotinib in the presence of PHA-665,752 (a MET TKI). The erlotinib-resistant mechanisms of these cells were analyzed. In addition, 33 autopsy tumor samples from 6 lung adenocarcinoma patients harboring multiple gefitinib-refractory tumors were analyzed.
HCC827ER developed MET amplification, and clinically relevant resistance occurred at ≥4-fold MET gene copy number gain (CNG). By contrast, HCC827EPR developed T790M without MET CNG. Of six patients harboring gefitinib-refractory tumors, three exhibited T790M only, one exhibited MET amplification only, and the other two exhibited T790M and/or MET amplification depending on the lesion sites. In these gefitinib-refractory tumors, T790M developed in 93% (14 of 15) of tumors without MET gene CNGs, in 80% (4 of 5) of tumors with moderate MET gene CNGs (<4-fold), and in only 8% (1 of 13) of tumors with MET amplification (≥4-fold).
These results indicate a reciprocal and complementary relationship between T790M and MET amplification and the necessity of concurrent inhibition of both for further improving patient outcomes.
A pulmonary artery aneurysm (PAA) is a rare condition. It is treated in various ways, depending on its location and size. Herein, we describe the preoperative diagnosis of a PAA that was resected by ...segmentectomy. A 44-year-old female underwent CT, which revealed a 15-mm saccular protrusion in the right pulmonary artery and was diagnosed with PAA. The patient was initially observed without requiring further treatment, but a gradual increase in size led to therapeutic intervention. Because the PAA was located just peripheral to the right A8 bifurcation, embolization using interventional radiology was deemed too difficult. Therefore, a surgical intervention was planned. Subsequently, S8 segmentectomy, basal segmentectomy, and basilar pulmonary artery ligation were all considered. Ultimately, basal segmentectomy was selected because it allowed the resection of the pulmonary artery and did not result in invalid ventilation of the basal segment. A basal segmentectomy was performed, and the PAA was safely removed without hemorrhage. Histopathological examination revealed arterial and venous wall-like areas, and the patient was diagnosed with pulmonary artery malformation. A PAA is typically treated with coil embolization, ligation of the pulmonary artery, aneurysmectomy, and lung resection; however, no clear treatment guidelines exist. After discussion, we selected basal segmentectomy as a safe and minimally invasive procedure, and we resected the PAA without complications. The optimal treatment strategy for PAAs varies according to location and size, and a careful treatment plan should be established.
Objective
We previously reported the noninferiority of paravertebral block (PVB) to epidural block. In this study, we assessed whether PVB via an intrathoracic approach was also safe for the patients ...ineligible for epidural block because of, for example, anticoagulation or antiplatelet therapy.
Methods
Patients admitted to our hospital for pulmonary resection between April 2010 and March 2012, and who were ineligible for epidural block for various reasons, were enrolled in this study. A catheter for PVB was inserted in the operative field by the surgeons just before closing the chest. Ropivacaine of 0.2 % was injected at 4 ml/h using an infuser pump for 5 days. Concurrent use of intravenous patient controlled analgesia (IVPCA) for 2 days with PVB was permitted as a post-operative analgesic at the discretion of anesthesiologists. We estimated the post-operative complications in these patients.
Results
A total of 35 (15.8 %) consecutive patients were enrolled in this study and successfully completed the study protocol. Thirty-two patients received concurrent IVPCA treatment. Post-operative complications due to PVB were not observed, but other complications included 1 incidence of atrial fibrillation, 1 hypertension, 1 pleural fluid accumulation, 1 respiratory failure requiring mechanical ventilation, and 1 of late chest pain requiring intercostal nerve block.
Conclusion
This study suggests that PVB is safe in patients ineligible for epidural block and can contribute to their pain relief following pulmonary resection procedure including video-assisted thoracic surgery.
Purpose
A paravertebral block (PVB) given via the surgical field can be safer and technically simpler than an epidural block (EP) for postoperative pain control. We conducted this clinical trial to ...confirm the effectiveness of PVB after thoracotomy.
Methods
In this non-inferiority trial, patients were randomly assigned to receive PVB (
n
= 35) or EP (
n
= 35). The primary endpoint was the pain assessed using the visual analog scale (VAS) at rest, 2, 24, and 48 h after thoracotomy, with the non-inferiority margin set at 15 mm. The secondary end points were the pain assessed using the VAS on exercising and on coughing, 2, 24, and 48 h after surgery, respectively, and the complications and need for additional analgesic agents.
Results
This trial revealed that PVB was not inferior to EP with respect to the primary end point: The mean VAS scores at rest, 2, 24, and 48 h after thoracotomy were 26.3, 10.8, and 8.3 mm in the PVB group and 23.6, 12.4, and 12.6 mm in the EP group, respectively (
P
< 0.01 for non-inferiority at all points). There were no significant differences between the groups in the incidence of complications or the need for additional analgesic agents.
Conclusion
PVB may replace EP for postoperative pain control because of its technical simplicity and safety.
We report a 27 years-old previously healthy male admitted to a psychiatric hospital because of abnormal behavior. He was suspected meningoencephalitis with fever, abnormal sweating, muscle tone, ...confusion, and introduced to the neurology department of our hospital. After admission, increasing convulsions and apnea attack required mechanical ventilation therapy. Anti-N-methyl-D-aspartate( NMDA) - receptor encephalitis was diagnosed based on positive (20-fold) anti-NMDA antibody in cerebrospinal fluid examination. An enhanced chest computed tomography (CT) showed a 43 mm cystic mass with calcification of the anterior mediastinum. He underwent the tumor resection under median sternotomy on the 18th hospital day. The plasmapheresis and steroid therapies were treated after the operation. The consciousness level gradually improved, the patient was withdrawn from the respirator on the post operative day( POD) 35, and transferred to a rehabilitation hospital on POD 60. The pathological result was mature teratoma. However, no specific findings such as inflammatory cell infiltration into nerve components were observed. Anti-NMDA receptor encephalitis was established by Dalmau in 2007 as encephalitis associated with ovarian teratoma. It presents mainly in young adult women with psychiatric symptoms, and requires mechanical ventilation management due to disturbance of consciousness, convulsions, and central hypoventilation in a short period of time. It presents severe symptoms in the acute phase and shows a unique clinical finding with a good prognosis even though it shows a protracted course. Treatment requires prompt tumor detection and early resection, as well as methylprednisolone (mPSL) pulse, plasmapheresis, and high-dose gamma globulin therapy. It is a neurological disease that requires emergency response, and the understanding and prompt response of related departments is important.
Although PDZK1 is a well-known adaptor protein, the mechanisms for its role in transcriptional regulation are largely unknown. The peroxisome proliferator-activated receptor alpha (PPARα) is a ...ligand-activated transcription factor that plays an important role in the regulation of lipid homeostasis. Previously, we established a tetracycline-regulated human cell line that can be induced to express PPARα and identified candidate target genes, one of which was PDZK1. In this study, we cloned and characterized the promoter region of the human
pdzk1 gene and determined the PPAR response element. Finally, we demonstrate that endogenous PPARα regulates PDZK1 expression.
Carcinoembryonic antigen (CEA) is a tumor marker widely used for nonsmall cell lung cancer (NSCLC). The aim of this study was to evaluate changes in serum CEA levels as a surrogate marker for tumor ...response to chemotherapy in NSCLC.
From 1995 through 2005, we retrospectively analyzed 24 NSCLC patients who had high serum CEA levels (>5 ng/ml) and who received chemotherapy followed by surgery. We compared serum CEA levels with tumor response, as defined by Response Evaluation Criteria in Solid Tumors (RECIST) or World Health Organization (WHO) criteria, as well as with histological response.
Serum CEA levels after chemotherapy significantly decreased in patients who achieved partial response, defined by RECIST or WHO criteria (p = 0.004 and p = 0.008, respectively), when compared with the CEA levels before chemotherapy. In contrast, there was no significant difference in CEA levels in patients with either stable disease or no response to chemotherapy. They decreased significantly, however, in patients in whom less than one-third of tumor cells was viable by pathological examination, but not in patients in whom more than a third was viable (p = 0.008). Using the receiver-operating characteristic (ROC) curve analysis, we found that a 60% reduction of CEA levels was an appropriate cutoff value in predicting a good response to chemotherapy. When the value was set at that level, the sensitivity of CEA for RECIST was 82%, and the specificity was 69%.
Serum CEA concentration was a useful surrogate marker for the evaluation of tumor response to chemotherapy and seemed to be comparable with RECIST in NSCLC patients who had elevated CEA levels prior to treatment.
We report a relatively rare surgical treatment for two cases of inflammatory pseudotumors of the lung. In case 1, a 52-year-old male with a history of left chest pain was admitted to our hospital for ...an abnormal nodule with an irregular margin that was detected in the left upper lung field. The nodule, measuring 15 mm in diameter, was larger than the one observed six months earlier, which had been removed by a thoracoscopic resection. In case 2, a 64-year-old female with a history of chronic cough and hemoptysis was admitted to our hospital, and an abnormal nodule with pleural indentation was detected in the lower left lung field. The nodule, measuring 8 mm in diameter, was also removed by a thoracoscopic resection. In both cases, the histologic examination enabled us to diagnose the lesion as an inflammatory pseudotumor. In general, it is very difficult to differentiate inflammatory pseudotumors from malignant tumors of the lung. The best treatment for inflammatory pseudotumors is usually early and complete surgical resection, since it can lead to improved survival. Therefore, we consider thoracoscopy-aided surgery to be less invasive and more useful than other surgical methods in the diagnosis and treatment of inflammatory pseudotumor of the lung.
When a 76-year-old woman was taken to a hospital by ambulance, she had a fever, was feeling fatigued and in dyspnea. She has a previous history of old myocardial infarct, ischemic cardiomyopathy, ...mitral valve replacement, tricuspid annuloplasty, MAZE operation, severe pulmonary hypertension, chronic congestive cardiac failure, and congestive liver. She was also undergoing a treatment for miliary tuberculosis using domiciliary oxygen therapy. Her chronic cardiac failure got worse, and congestive liver and jaundice also got worse. Thoroughly examining her condition, we found that she had an approximately 6 cm saccular aneurysm in her left external iliac artery. From the fact that a previous CT examination a year before didn't detect any arterial aneurysm, we assumed her aneurysm was an infected external iliac artery aneurysm. She has been physically weakened and debilitated before the surgery. We first performed an extra-anatomic revascularization by bypassing the right external iliac artery to the left common femoral artery. And then, we performed a percutaneous arterial embolization with coils for the infected external iliac artery aneurysm. After the surgery, she recovered well and left the hospital. A year has passed now after the surgery, the left external iliac artery aneurysm remains occluded and no infection is seen. This surgery is one of the effective options for a patient who is physically weakened and debilitated with an infected iliac artery aneurysm.
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