Objective. The aim of this study was to evaluate the effectiveness and frequency of acute respiratory deterioration after second-line chemotherapy in patients with interstitial pneumonia associated with lung cancer. Methods. The records of 44 patients with lung cancer complicated by interstitial pneumonia treated between April 2004 and April 2013 were retrospectively evaluated in order to determine the clinical characteristics, second-line chemotherapy regimens and frequency of acute respiratory deterioration after second-line chemotherapy. Results. Acute respiratory deterioration after anti-cancer therapy was noted in eight of the 44 (18.2%) patients, five (62.5%) of whom died of respiratory failure. The frequency of acute respiratory deterioration among the patients treated with second-line chemotherapy was higher than that among the patients treated with first-line chemotherapy (8 of 80, 10%). The response rate and median progression-free survival after second-line chemotherapy were 0% and 1.4 months for small cell lung cancer and 3% and 1.8 months for non-small cell lung cancer, respectively. Conclusions. Acute respiratory deterioration is a frequent complication of second-line chemotherapy. Because the clinical effectiveness of second-line chemotherapy regimens was poor in the patients with lung cancer associated with interstitial pneumonia in the present study, the risks and benefits of such regimens should be carefully considered in this subgroup.

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Objective. We evaluated the usefulness of assessing the hyaluronic acid (HA) level in pleural fluid for the differential diagnosis of malignant pleural mesothelioma (MPM). Methods. The data regarding the pleural fluid HA concentration were retrospectively collected from Rosai Hospitals and related facilities in Japan. Results. A total of 860 cases were examined, which included 139 cases of MPM, 76 of benign asbestos pleurisy (BAP), 324 of lung cancer (LC), 74 of other malignant conditions (OMC), 120 of infectious pleuritis (IP), 11 of collagen diseases (CD) and 116 cases had other conditions. The median (range) HA concentrations in the pleural fluid were 76,650 (211-33,000,000) ng/ml in the MPM cases, 28,000 (165-152,000) ng/ml in the BAP, 19,000 (800-134,000) ng/ml in the LC, 12,200 (900-157,200) ng/ml in the OMC, 23,400 (900-230,000) ng/ml in the IP, 17,800 (9,000-80,800) ng/ml in the CD and 11,575 (23-90,000) ng/ml in patients with other diseases. The HA levels were significantly higher in MPM cases than in the patients with other diseases. The receiver operating characteristics (ROC) analysis revealed an area under the ROC curve value of 0.818 (95% confidence interval, 0.772-0.864) for the differential diagnosis of MPM. With a cut-off value of 100,000 ng/ml, the sensitivity was 44.5% and the specificity was 98.2%. These results indicate that MPM should be strongly suspected in cases with an elevated concentration of pleural fluid HA. Conclusion. The pleural fluid HA concentrations might be useful for the differential diagnosis of MPM.

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Background. Myocardial metastasis from various malignancies, including primary lung cancer, is rarely diagnosed before death. Case. A 75-year-old woman was diagnosed as having synchronous simultaneous quadruple malignancies, including bilateral primary lung cancer, malignant lymphoma and rectal cancer. After receiving chemotherapy for the lymphoma, she underwent bilateral pulmonary resection and postoperative adjuvant chemotherapy in addition to low anterior resection of the rectum. One year later, the right lung cancer recurred in the right hilar lymph node. The patient therefore received radiation therapy to the recurrent lesion, followed by supportive care alone. She subsequently visited our outpatient clinic with a complaint of dyspnea. A chest radiograph showed cardiac dilatation, electrocardiography showed ST-T elevation in V2-V3 and cardiac ultrasonography showed multiple hypoechoic areas throughout the anterior to lateral wall of the left ventricle, resulting in a diagnosis of myocardial metastasis. The patient was hospitalized and treated with diuretics and digitalis; however, she died five days after hospitalization. An autopsy showed tumor infiltration into the myocardium at multiple sites; the location of these lesions coincided with that of the hypoechoic areas previously observed on ultrasonography. The pathological examination revealed the intramural cardiac lesions to be metastases of the right lung adenocarcinoma. Conclusions. We herein reported an uncommon case of myocardial metastasis in a patient with quadruple malignancies diagnosed on electrocardiography and echocardiography before death and confirmed at autopsy.

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Background. Honeycomb lung is primarily observed in patients with progressive idiopathic pulmonary fibrosis (IPF). Case. A 63-year-old man reported to our hospital for an assessment of honeycomb-like changes in the right lung lower lobe detected on chest computed tomography (CT). IPF was diagnosed based on the imaging findings and elevation of the serum KL-6 level. The patient subsequently underwent bronchoscopy, as the honeycomb-like changes were unilateral and there was no evidence of malignancy. The findings suggested atypical IPF, and he remained under observation. Six months after the bronchoscopy procedure, chest CT showed an increase in the size of the nodule in the honeycomb-like tissue, and the patient underwent right lower lobectomy. The pathological analysis of the surgical specimen showed the infiltration of cancer cells with fibrosis in the nodule extending from the region of the right lower lobe that corresponded to the area identified on chest CT. The honeycomb-like tissue was confirmed to be well-differentiated adenocarcinoma and displayed an alveolar replacement pattern in the emphysematous lung. Fibrosis with alveolar collapse and muscularization, a characteristic finding of interstitial pneumonia, was not observed. Conclusions. The present findings suggest that honeycomb-like changes on CT may be caused by well-differentiated adenocarcinoma in the emphysematous lung.

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Background. Lung cancer metastasis to the small bowel has a poor prognosis, and long-term survival is extremely rare. We herein report a case of long-term survival after surgical resection for small bowel metastasis of lung cancer. Case. A 68-year-old man underwent left upper lobectomy for lung cancer, which was diagnosed on pathology as pleomorphic carcinoma, T1bN0M0, Stage IIA. He subsequently developed bloody stools and anemia six months after pulmonary resection. Abdominal computed tomography revealed intussusception of the small bowel, and a small bowel tumor was detected on upper gastrointestinal endoscopy. Partial resection of the jejunum was consequently performed. On pathology, the tumor was diagnosed as a metastatic lesion of the lung pleomorphic carcinoma; therefore, four cycles of platinum doublet chemotherapy were administered postoperatively. The patient remains alive without recurrence four years and nine months after undergoing resection of the small bowel tumor. Conclusions. Patients with small bowel metastasis of lung cancer have a poor prognosis. However, it has been reported that resection of the lesions may improve the quality of life (QOL) and prolong survival in extremely rare cases. Therefore, the possibility of surgical treatment in patients with bowel metastasis of lung cancer should be discussed positively.

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Background. It is difficult to distinguish the development of granuloma along the staple line after segmentectomy from tumor recurrence. Case. A 70-year-old male underwent left S⁸ segmentectomy with lymph node dissection for early stage IA lung adenocarcinoma using video-assisted thoracic surgery. One year later, a routine chest CT scan disclosed a mass adjacent to the previous segmentectomy site. Although local recurrence of lung cancer was suspected, a bronchoscopic examination showed no recurrence, and the results of a bacteriological examination were nonspecific. Steroid therapy was therefore initiated based on our concern for the potential of organizing pneumonia. The mass lesion subsequently shrank in size, almost disappearing. Interval chest CT, however, demonstrated regrowth of the site of consolidation along the staple line. The steroid therapy was repeated; however, the area of consolidation continued to grow. Completion left lower lobectomy was thus performed, as the possibility of local cancer recurrence could not be excluded. At the time of thoracotomy, a hard white mass was palpated along the staple line in the left lower lobe. A pathological analysis revealed epithelioid granuloma with caseating necrosis, and Mycobacterium avium complex (MAC) grew from a culture of the specimen. Therefore, the lesion was thought to be a granuloma caused by MAC infection at the previous segmentectomy staple line. Conclusions. We herein report a rare case of pulmonary granuloma associated with non-tuberculous mycobacteriosis occurring at the staple line after segmentectomy for lung cancer. In addition to local recurrence or secondary primary lung cancer, the possibility of mycobacterial granuloma should be considered in cases in which pulmonary nodules are detected on the staple line after pulmonary resection.

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Background. Pulmonary carcinosarcoma is a rare malignant neoplasm composed of a mixture of carcinoma and sarcoma containing ectopic components, including malignant cartilage, bone and skeletal muscle. Case. The patient was a 71-year-old man who developed nighttime wheezing. Chest computed tomography (CT) revealed a 5.5-cm tumor shadow in the right lower lobe, although a definitive diagnosis was not reached on bronchoscopy. The patient subsequently underwent resection of the right lower lobe and mediastinal lymph node dissection for suspected lung cancer, and a pathological examination revealed pulmonary carcinosarcoma with mixed components of squamous cell carcinoma and fetal adenocarcinoma as well as sarcoma-like components with cartilage and osteoid. The patient is currently alive without relapse at two years and three months postoperatively. Conclusions. Carcinosarcoma progresses quickly and has a poor prognosis; however, most patients who undergo complete surgical resection achieve long-term survival. Further research with respect to surgical treatment and chemotherapy for pulmonary carcinosarcoma is thus required.

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Background. Lung cancer is occasionally accompanied by hypertrophic pulmonary osteoarthropathy (HPO) as a paraneoplastic syndrome. Case. We herein report the case of a 49-year-old man with stage IIIB pulmonary squamous cell carcinoma associated with HPO. The patient complained of clubbing of all fingers and toes and bilateral knee joint pain that had not been alleviated by treatment with a non-steroidal anti-inflammatory drug. Chest X-ray and chest CT scans showed a giant mass in the right upper lung field, and bone scintigraphy demonstrated an abnormal symmetrical uptake of radioisotope in the distal end of the long bones of the upper and lower extremities. We therefore diagnosed the patient with HPO, and his clinical symptoms improved after right upper lobectomy. An immunohistochemical study of the tumor cells was positive for vascular endothelial growth factor-A (VEGF-A). The high level of serum VEGF-A observed preoperatively decreased to the normal range after three weeks, and follow-up bone scintigraphy showed the disappearance of uptake. Adjuvant chemotherapy and radiotherapy were added to the treatment regimen, and there have since been no findings of recurrence as of 20 months after the surgery.

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Background. We herein report a case of lung adenocarcinoma with gefitinib-resistant carcinomatous meningitis exhibiting dose-dependent effects of erlotinib. Case. A 68-year-old non-smoking female was diagnosed with lung adenocarcinoma, cT1bN3M1b, cStage IV and found to be positive for an epidermal growth factor receptor gene mutation (Exon 21: L858R). She was treated with gefitinib and achieved a partial response (PR). Although the CEA level gradually became elevated after 10 months of treatment, we continued the gefitinib therapy because no lesions were classified as demonstrating progressive disease (PD). The patient was subsequently admitted to our hospital due to vomiting and anorexia. The spinal fluid displayed an increased protein level and decreased glucose level, whereas no CEA elevation or atypical cells were observed. Brain MRI showed findings indicative of brain metastasis, with meningeal dissemination in the basal ganglia. Therefore, we comprehensively diagnosed the patient with carcinomatous meningitis and changed the treatment regimen from 250 mg of daily gefitinib to 150 mg of daily erlotinib. Within one week, her symptoms improved and the CEA level declined. However, we again decreased the daily dose of erlotinib from 150 mg to 100 mg due to a severe rash. Unfortunately, her headache worsened and the CEA level again became elevated; therefore, we increased the dose to 125 mg and 150 mg, after which the patient's symptoms improved and the CEA level decreased. Conclusions. This case suggests that adequate treatment with erlotinib improves carcinomatous meningitis in patients resistant to gefitinib.

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Background. Cellular schwannomas are characterized by a high density of spindle cells, as in the Antoni A pattern. Case. A 65-year-old female was referred to our hospital for an evaluation of back pain. A CT scan showed a giant tumor, 12 cm in size, superior to the right crus of the diaphragm. An FDG-PET scan revealed abnormally increased FDG uptake in the tumor. A malignant tumor was suspected, so the tumor was resected. The tumor was encapsulated, with a smooth peripheral sheath, and was strongly adherent to the vertebrae and descending aorta. The histological examination showed that the spindle cells had a high-density arrangement with the accumulation of foamy macrophages. Immunohistochemical staining showed that the spindle cells were positive for the S-100 protein and the Ki-67 labeling index was low. The final diagnosis was a cellular schwannoma. Conclusion. We herein report a case of a giant cellular schwannoma originating from the phrenico-costal sinus. Discriminating the schwannoma from a malignant soft tissue tumor was required, because the lesion showed an abnormally increased FDG uptake due to its high cell density.

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The early detection of lung cancer is crucial for reducing the mortality of lung cancer. In the US, where routine screening is not conducted, about 60% of cases of lung cancer are detected in the advanced stage. In contrast, in Japan, lung cancer is primarily found in the early stage on X-ray screening. Consequently, the five-year survival rate of patients with early lung cancer in Japan is as high as 83.2%, and reductions in the mortality rate have been demonstrated in case-control studies performed by multiple centers. However, the rate of screening for lung cancer on chest X-rays has decreased in recent years, and the number of cases detected in the early stage is therefore declining. In addition, the rate of detection has also been reduced by the decrease in the use of sputum cytology examinations to detect hilar lung cancer. Furthermore, low-dose CT screening is not expected to be more effective than the existing screening method using chest radiography. Therefore, it is necessary to achieve greater reductions in mortality associated with lung cancer by encouraging further screening among the public.

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Stereotactic body radiotherapy (SBRT) is an important treatment option for inoperable patients with stage I non-small cell lung cancer, especially elderly patients, the number of which is currently increasing. An impaired pulmonary function itself is not a contraindication for SBRT; however, interstitial pneumonia should be treated with care, as it is a significant risk factor for severe radiation pneumonitis after SBRT. The use of SBRT in cases of centrally located tumors also requires special care due to the potential for severe toxicity. Multi-institutional trials of SBRT have demonstrated a local control rate of 90% and 3-year overall survival rate of 60% among inoperable patients. Therefore, it is necessary to accumulate further evidence and develop new therapies in order to improve outcomes, reduce toxicities and expand SBRT indications.

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Objective. As the use of surgical robots has become widespread, it is necessary to verify their usefulness in the field of general thoracic surgery. We herein discuss the current status and future prospects of robotic surgery for lung cancer. Materials and Methods. We analyzed reports in the literature as well as our experience with robotic surgery in order to verify the usefulness of and current problems associated with these devices in patients with lung cancer. Results. The most favorable advantage of robotic surgery is the markedly free movement of joint-equipped robotic forceps under high three-dimensional vision. Accurately operating the robot makes complex procedures straightforward and may help to overcome the weak points of previous thoracoscopic techniques. Robotic surgery has been safely introduced into the field of thoracic surgery with favorable initial results. The efficiency and safety of robotic procedures will improve with the acquisition of skills. Conclusions. Although current evidence is insufficient to support the widespread use of robotic devices in thoracic surgery, this technology may be extended to thoracoscopic surgery, and reports showing its usefulness in patients with primary lung cancer have been accumulating. Preparing for the application of robotic surgery in advanced medical care and obtaining coverage under the national health insurance program are urgent issues.

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Objective. As endoscopic treatment is extensively employed to treat central type early-stage lung cancers, the ability to detect such lesions is becoming more important. However, diagnosing flat type lesions using conventional bronchoscopy is difficult in cases involving subtle mucosal changes. Therefore, improving the rate of detection of intraepithelial lesions is clinically desirable. Methods. The clinical usefulness of autofluorescence bronchoscopy (AFB) was evaluated by reviewing previous reports and the authors' experience. Results. There were no significant differences in the sensitivity of detecting invasive cancers between conventional bronchoscopy and AFB. However, AFB demonstrated higher sensitivity in cases of early cancer and atypical squamous cell lesions, which may contribute to improving the diagnosis. Mucosal invasion was clearly observed on AFB, which may provide useful support for endoscopic treatment. Conclusions. The combined use of conventional bronchoscopy and AFB is recommended for diagnosing and treating central type early-stage lung cancer.

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Small lung tumors with ground glass opacity (GGO) are often not palpable during surgery. Therefore, identifying and localizing these lesions is a major challenge in the field of general thoracic surgery. To date, a number of strategies for detecting such lesions have been reported, although each has advantages and disadvantages. Intraoperative ultrasound and the Endofinger are non-invasive tools for isolating small lung tumors, although the accuracy of these devices for identifying GGO lesions is controversial. Reported preoperative lung marking techniques using percutaneous CT-guided needle puncture include the placement of a hook wire and injection of dye or Lipiodol^®. Although these techniques are relatively concise, the number of areas suitable for percutaneous needle puncture is anatomically limited, and there are concerns regarding complications, such as pneumothorax, apparatus dislodgement (especially the hook wire) and potentially fatal air embolism. Peribronchial marking techniques include the injection of dye, barium or Lipiodol. These strategies are considered to be relatively safe, although, if marking is conducted under CT guidance, the setup may be troublesome and excessive radiation exposure for the bronchoscopist is a problem. Recent advances in virtual bronchoscopy may overcome these limitations. We recently reported a novel strategy, termed virtual-assisted lung mapping (VAL-MAP), which is an extension of the bronchoscopic technique. In VAL-MAP, multiple markings are made on the lung surface by bronchoscopically injecting dye under fluoroscopy with the guidance of virtual bronchoscopy. These markings provide " geometric information" on the lung surface. Beyond the conventional concept of " lung marking", VAL-MAP is expected to play a role as an intraoperative navigation system in the field of general thoracic surgery by allowing the surgeon to set precise resection lines in patients undergoing lung wedge resection and/or complex segmentectomy.

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Transbronchial biopsies are often employed to definitively diagnose peripheral pulmonary lesions. Although this technique is associated with fewer complications than percutaneous biopsies, the diagnostic yield is low and the method requires the bronchoscopist to guide the bronchoscope and biopsy instruments to the lesion. Virtual bronchoscopic navigation (VBN), an exclusive system of which is now commercially available, can be used to guide the bronchoscope to peripheral lesions under direct visualization using virtual bronchoscopy images of the bronchial route. VBN is applied in combination with CT-guided ultrathin bronchoscopy, endobronchial ultrasonography with a guide sheath (EBUS-GS) and fluoroscopy- and non-fluoroscopy-assisted bronchoscopy, with a reported rate of diagnosis of peripheral pulmonary lesions and tumors measuring 2 cm or smaller of 74% and 67.5%, respectively. In a randomized controlled study, the combination of VBN and EBUS-GS increased the diagnostic yield, while that combined with ultrathin bronchoscopy improved the rate of diagnosis of lesions located in the right upper lobe or peripheral third of the lung field and those invisible on posterior-anterior radiographs, according to a subanalysis. In order to increase the diagnostic yield of VBN, it is important to clarify the relationship between the lesion and the extracted bronchus used to construct virtual bronchoscopic images on CT and select the appropriate combination bronchoscopy procedure. VBN is a useful method for supporting bronchoscopy whose further spread and advancement is desirable.

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Objective. Percutaneous radiofrequency ablation with CT guidance is an innovative treatment for lung malignancy that was first introduced worldwide in 2000. We herein evaluated the effectiveness of this treatment in patients with clinical stage I lung cancer and summarize the principles, characteristics, indications and practical issues associated with radiofrequency ablation for lung malignancy. Methods. We analyzed 50 nonsurgical patients (29 males and 21 females; mean age, 74.7 years) with clinical stage I (IA, n=38; IB, n=12) histologically proven non-small cell lung cancer who underwent percutaneous radiofrequency ablation with CT guidance. A total of 52 tumors were treated with 52 ablation sessions. Results. The median follow-up period was 37 months. Local progression was observed in 16 (31%) of the 52 tumors. The overall, cancer-specific and disease-free survival rates were 94%, 100% and 82% at one year, 86%, 93% and 64% at two years and 74%, 80% and 53% at three years, respectively. Therefore, radiofrequency ablation of clinical stage I non-small cell lung cancer provides promising patient survival outcomes, although local efficacy must be improved. Radiofrequency ablation for lung cancer is usually performed under local anesthesia and requires only a short hospital stay. Complications related to the procedure are generally not serious, indicating that this treatment is less invasive than surgery. However, based on our experience, lung tumors measuring more than 2 cm in diameter are not well controlled using radiofrequency ablation alone. Conclusions. Since there are currently no randomized controlled clinical studies comparing radiofrequency ablation and surgery or stereotactic irradiation therapy for lung cancer, the data of retrospective cohort studies are primarily referenced in published papers. This is one reason why this treatment is not well accepted in the field of lung cancer therapy. However, radiofrequency ablation has the potential to be used as an alternative therapy for lung cancer in cases in which surgery or stereotactic irradiation therapy are contraindicated.

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In the General Rules for Clinical and Pathological Record of Lung Cancer, 7th edition, early lung cancer is defined as squamous carcinoma in the central airway, whereas there is no definition for early lung adenocarcinoma. Noguchi et al. reported that the subset of small adenocarcinoma, i.e. localized bronchioloalveolar carcinoma without active fibroblastic foci, is amenable to therapy, with a 5-year survival of almost 100%. These lesions may be called early lung adenocarcinomas. On lung CT images, such lesions appear as pure ground-glass nodules or partly solid ground-glass nodules, collectively called subsolid nodules (SSNs). For example, the radiological differential diagnosis of SSN should include organizing pneumonia and atypical adenomatous hyperplasia. The rate of incidentally discovered SSN has recently increased due to the wider availability of CT scanners, and the detection of multiple SSNs in a single patient is not rare. The recommendation statement issued by the Fleischner Society in 2013 provides follow-up/treatment strategies for cases of solitary or multiple SSNs. However, these recommendation statements are based largely on expert opinion, rather than the results of clinical studies, due to the lack of solid evidence regarding various important issues in SSN management. Nevertheless, the recommendations are reasonable and readily applicable to clinical practice. This article summarizes these recommendations below.

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The number of elderly lung cancer patients in Japan has recently been increasing due to the effects of a super-aging society. Moreover, amid the increase in the identification of early lung cancer patients following the widespread adoption of screening examinations, the need for minimally invasive surgical procedures has further increased. In other words, limited operations have come to the forefront. Original thoracoscopic techniques for treating lung cancer differ only in terms of the level of access to the pleural cavity, with thoracoscopic surgical maneuvers being carried out in the same manner as that during conventional surgery. However, the ability to perform thoracoscopic surgery while watching a video monitor without ever directly coming into contact with tissue is a new surgical method that goes far beyond the conventional concept of surgery and can be described as a qualitatively different form of surgical intervention. Thoracoscopic surgery is a surgical method that imposes little physical stress on the patient, while shortening the time required to return to society, and has aesthetic advantages. Nevertheless, as one false move may result in a major accident, regular and persistent training is required. For this purpose, a variety of approaches have been developed to allow surgery can be conducted using superior instruments in a better environment, and the further development of newer, safer thoracoscopic procedures is in demand from thoracic surgeons.

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