Objective and Method. We examined the changes in the EGFR mutation status, including the frequency of acquired T790M mutations, in 25 non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutations who underwent a re-biopsy (include pleural effusion) from January 2013 to March 2015. Results. The male:female ratio was 7/18, at the time of the initial chemotherapy the median age was 67 years (range, 33-77), the types of EGFR mutation included exon19 del (n=12), L858R (n=11), L858R+T790M (n=1), and T751-I759 del ins N (n=1). Eighteen patients were treated with gefitinib as first-line treatment, and 12 patients underwent a re-biopsy just before the administration of a second-line treatment. The biopsy sites at the initial examination were the primary lung tumor (n=21), pleural dissemination (n=1), the bone (n=2), and pleural effusion (n=1). The biopsy site at re-biopsy was the primary tumor (n=9), pleural effusion (n=15), and the lymph nodes (n=1). At re-biopsy, 10 patients (40%) had acquired the T790M mutation. In four cases that received a biopsy using a bronchoscope, the results between the specimen and a mutation analysis were discordant. Conclusion. The presence of a resistance gene affects the choice of subsequent treatment. However, the ability to perform a genetic analysis using biopsied tissue samples is limited. We should therefore consider the use of cytology specimens, including fluid samples.
Background. The safety of administering alectinib to patients who develop crizotinib-induced liver dysfunction and skin eruption is unclear. Case. A 65-year-old female patient underwent video-assisted right upper lobectomy and mediastinal lymph node dissection after being diagnosed with lung adenocarcinoma (cT1aN0M0 Stage IA). She was treated with post-operative adjuvant chemotherapy for pT1aN2M0 Stage IIIA and subsequently developed mild liver dysfunction. At three years after surgery, cancer was found to have recurred in the mediastinal lymph nodes; an EML4-ALK genetic test performed using the surgical specimens was positive. At approximately one week after the initiation of crizotinib treatment, liver dysfunction and a drug eruption occurred. We therefore reduced the dose and began alternate-day dosing; however, crizotinib was discontinued because the patient showed no improvement. The administration of alectinib was then started after radiation therapy because the patient's serum level of CEA was elevated and the tumor was increasing in size. After the administration of alectinib, tumor shrinkage was observed and a normal liver function was achieved. As a result, the alectinib treatment was continued. Conclusion. The administration of alectinib was found to be safe and effective in a patient who demonstrated drug eruption and liver dysfunction after the administration of crizotinib.
Background. Nephrotic syndrome is frequently observed as paraneoplastic syndrome in the patients with malignant disease. However, malignant pleural mesothelioma with nephrotic syndrome is rare. The therapeutic approaches for malignant pleural mesothelioma with nephrotic syndrome are not yet well established. Case. A 65-year-old man was admitted with dyspnea on exertion due to the left pleural effusion. A video-assisted thoracoscopic surgical pleural biopsy failed to make a diagnosis. Five months later, he was admitted to our hospital with abdominal pain and systemic edema, and was diagnosed as having nephrotic syndrome with massive proteinuria (36.6 g/day). A kidney biopsy revealed that the cause of nephrotic syndrome was membranous nephropathy and he was treated with high-dose steroids. It was suspected that his condition was complicated with a malignancy and PET-CT showed the accumulation of 18F-FDG in the thick pleura on the left mediastinum side. He underwent open pleural biopsy and was diagnosed with epithelial malignant pleural mesothelioma. He could not undergo surgical resection due to his low serum albumin level and because he had been treated with high-dose steroids; he therefore received chemotherapy. After 5 cycles of chemotherapy, his serum albumin level improved and his dose of steroids had decreased, thereby enabling pleurectomy/decortication. The patient's serum albumin level and proteinuria were further improved after the surgical resection of the tumor. Conclusion. We experienced a case of malignant pleural mesothelioma with paraneoplastic nephrotic syndrome, which was improved by chemotherapy and surgical resection.
Background. Small cell lung cancer arises in the central airway and exhibits a poor prognosis. We herein report a case of small cell lung cancer mainly composed of pleural thickening that caused acute exacerbation of interstitial pneumonia after amrubicin treatment. Case. A 62-year-old man was diagnosed with interstitial pneumonia in 2009. He was admitted to our hospital due to a fever and cough from February 2014, and a chest X-ray showed pleural thickening of the left upper lung. After CT-guided lung biopsy, small cell cancer was diagnosed. The patient received chemotherapy, consisting of six cycles of cisplatin and etoposide. After showing a partial response to the treatment, the patient was followed up as an outpatient. He developed a fever at the beginning of the October 2014, and a chest X-ray revealed local recurrence. The patient received second-line chemotherapy with amrubicin. However, he developed a fever in the middle of October 2014, and computed tomography of the chest showed acute exacerbation of interstitial pneumonia due to amrubicin. The patient was treated with steroid pulse therapy, and his condition improved. However, the small cell lung cancer progressed rapidly, and the patient eventually died. Conclusion. Small cell lung cancer which rapidly progresses through the pleura has a poor prognosis. Cases such as the present of small cell lung cancer with interstitial pneumonia should be carefully treated by chemotherapy due to the possibility of its acute exacerbation.
Background. As the incidence of lung cancer and pulmonary non-tuberculous mycobacterial (NTM) infection is increasing, the incidence of coexistent lung cancer and pulmonary NTM infection is also increasing. Evidence shows that drug interactions can be problematic in the treatment of coexisting lung cancer and pulmonary NTM infection. Gefitinib is normally used to treat lung cancer. However, CYP3A4 inducers, such as rifampicin and rifabutin, reduce the concentration of gefitinib in the blood, whereas CYP3A4 inhibitors, such as clarithromycin, increase its concentration. Consequently, drug interaction is a major problem when gefitinib is used to treat lung cancer in patients with progressive pulmonary NTM infection. Case. A 72-year-old man was diagnosed with stage IV lung cancer. The cancer was pathologically identified as an adenocarcinoma, and a driver mutation of the epidermal growth factor receptor (L858R) was identified. The patient was treated with gefitinib, but he subsequently developed a progressive pulmonary Mycobacterium avium infection. We also identified drug interactions between gefitinib and rifampicin, rifabutin and clarithromycin. The patient's blood gefitinib concentration was measured because combination therapy with these drugs can lead to instability in the concentration of gefitinib and tumor progression. The gefitinib concentration was reduced to 60% of the original concentration following the administration of rifabutin but increased to 130% of the original concentration after the administration of rifabutin, clarithromycin, and ethambutol. However, the patient developed hyperbilirubinemia after the combined administration of rifabutin, clarithromycin, and ethambutol, and as a consequence, the combination therapy was discontinued. Afatinib is a drug that is largely considered to be unaffected by the CYP3A4 metabolism. Thus, afatinib was administered with clarithromycin, ethambutol, and rifampicin; however, the patient experienced side effects and the therapy was discontinued. Conclusion. We herein presented a case of a patient with coexisting lung cancer and pulmonary Mycobacterium avium complex disease, who was treated with gefitinib, rifabutin, clarithromycin, and ethambutol. However, this combination therapy resulted in both drug interactions and side effects. It is therefore very important to consider drug interactions and side effects in the treatment of coexisting lung cancer and pulmonary NTM infection.
Background. The prognosis of carcinomatous meningitis associated with lung cancer is very poor. There are few reports of hydrocephalus secondary to carcinomatous meningitis, and no standard therapy has been established. Case. A 35-year-old woman who had received medical therapy for miliary tuberculosis five years previously presented to us with multiple nodular lesions in the lungs and brain. She was diagnosed with lung adenocarcinoma, cT4N2M1b, stage IV, with carcinomatous meningitis, and was started on treatment with whole-brain irradiation and oral gefitinib. Six weeks later, as the carcinomatous meningitis had worsened, the medication was changed to erlotinib. One year later, the pulmonary tumors had also worsened, and the patient was started on systemic chemotherapy with carboplatin, pemetrexed, and bevacizumab. She developed hydrocephalus, so erlotinib treatment was resumed, and a ventriculo-peritoneal shunt was placed. These treatments resulted in a marked improvement in her performance status, and the patient survived for two years and six months after the diagnosis. Conclusion. We encountered a patient with lung adenocarcinoma and carcinomatous meningitis in whom EGFR-TKI therapy and ventriculo-peritoneal shunt placement proved effective.
Background. Primary lung cancers commonly invade the lung parenchyma and, on reaching the visceral pleura, cause pleural dissemination. We herein report a surgical case of primary lung cancer which showed a unique growth pattern of spreading predominantly within the interlobular pleura. Case. A 65-year-old male patient was referred to our department because of an abnormal shadow in the right middle lung field detected on chest X-ray film during the follow-up period of angina. Contrast-enhanced computed tomography revealed slightly enhanced nodule shadows with a beaded appearance in the right minor and major fissures. During the observation period, the size of this abnormal shadow increased slowly with no evidence of lymph node enlargement or distant metastasis. Therefore, the patient underwent surgical resection (right upper and middle lobectomy with partial resection of the right lower lobe) for diagnostic and therapeutic purposes, and lymph node dissection was performed. On a histopathological examination, the tumor was found to be located only partly within the lung parenchyma of the upper lobe but predominantly within the interlobular pleura. The tumor cells were arranged in a tubular or papillary pattern, and immunohistochemical examinations revealed the tumor cells to be positive for TTF-1 and SP-A, leading to a diagnosis of primary pulmonary adenocarcinoma (pT3N0M0). In addition, EML4-ALK translocation was positive, whereas EGFR mutation was negative. The patient received adjuvant chemotherapy with the oral administration of UFT for two years after surgery with no evidence of recurrence. Conclusion. The invasive growth of primary lung cancer within the interlobular pleura is a rare form of progression. In our present case, it was difficult to distinguish between primary lung cancer and other lesions of pleural origin.
Background. Chondrosarcoma often originates in the femur and pelvis and rarely in the lungs. In Japan, to date, only 18 cases have been reported, including the present case. Case. The patient was a 53-year-old man who regularly consulted a local physician for hypertension and dyslipidemia. One month prior to the initial examination, the subject experienced coughing and was examined by his primary care physician. Upon the identification of a shadow that indicated a mass in the right lower lobe of the lung on a chest X-ray, the subject was referred to our department and was hospitalized for close examination. Chest CT revealed a mass spanning the right middle and lower lobes; however, bronchoscopy did not lead to definite diagnosis. A malignant tumor was suspected on the basis of MRI and FDG-PET. Thus, right middle and lower lobectomy was performed. The histopathological analysis of the resected specimen revealed the growth of chondrocyte-like tumor cells with irregular atypia in large volumes of hyaline cartilage-like substrate, which led to the pathological diagnosis of chondrosarcoma. On the basis of the results of a whole body examination, pulmonary metastasis from other organs was ruled out and pulmonary chondrosarcoma was diagnosed. The patient's postoperative progress has been favorable, and at present, the patient is progressing without recurrence or primary lesions in other organs. Conclusion. We experienced the case of a patient with chondrosarcoma, which was considered to have originated in the lungs. In such cases, the recommended first-line treatment is total surgical resection. The prognosis following complete resection is generally good. However, recurrence is common; thus, such cases require careful follow-up, similar to the present case.
Background. We report a case of salvage surgery for lung cancer with the treatment of brain metastases and 3 years of maintenance chemotherapy. Case. A 55-year-old woman consulted a hospital complaining of headache, dizziness and speech disorder. She was diagnosed with two brain tumors and underwent surgical resection for one of them. The pathological examination of the excised brain tumor revealed adenocarcinoma, and chest computed tomography (CT) also revealed a lung tumor invading the mediastinal pleura in the left upper lobe. She was diagnosed with lung cancer (cT3N0M1b, stage IV). Gamma knife radiosurgery was performed for the other metastatic brain tumor. After undergoing treatment for her brain metastases, she was introduced our hospital for lung cancer treatment. She received 4 cycles of combination chemotherapy with cisplatin (CDDP) and pemetrexed (PEM) followed by 3 years (40 cycles) of maintenance chemotherapy with PEM. The lung tumor remarkably diminished, and no regrowth or new metastasis was observed during the period of maintenance chemotherapy. We therefore performed left upper lobe lobectomy as salvage surgery. The pathological examination of the excised lung tumor revealed no viable cells. The patient's postoperative course was uneventful and no recurrence was found at 11 months after surgery. Conclusion. We experienced a case of salvage surgery for lung cancer after long-term maintenance chemotherapy with PEM and the treatment of multiple brain metastases. Salvage surgery should be indicated for patients who undergo long-term maintenance chemotherapy.
Background. Cavitary lesions rarely form in patients with lung cancer, and thin-walled cavities are particularly rare. Case. A 55-year-old man had suffered from a lung abscess; a previous chest CT scan had already revealed a 14-mm cystic lesion in S2a of the right lung. Three years later, he was re-admitted to our hospital because the cystic lesion in the right S2 had increased in size. A chest CT scan on admission showed a large, 77-mm mass shadow with thin-walled cavitation in the right S2-S6, with partial hypertrophy on the caudal side and many intrapulmonary nodules with thin-walled cavitation. Transbronchial biopsy revealed squamous cell carcinoma. After three cycles of chemotherapy with cisplatin and docetaxel, the wall of the primary lesion and almost all of the metastases had become thinner, resulting in cyst-like shadows. While a number of hypotheses have been proposed regarding the mechanism behind thin-walled cavitation in lung cancer, we suspected that the thin-walled cavity in the present case developed through a check valve mechanism. Conclusion. Careful follow-up is indispensable in patients with pulmonary thin-walled cavities due to the possible development of lung cancer.
Background. Nivolumab has recently been approved for non-small cell lung cancer, due to its benefits as a second-line chemotherapy. However, drug-induced lung disease (DILD) has been reported as a notable side effect. Case. A 49-year-old man had received treatment with nivolumab as a seventh-line chemotherapy for adenocarcinoma of the lung. Eight days after the first administration, he suffered from fever and hypoxia, and a ground-glass opacity was revealed on a chest CT scan. The symptoms were attributed to DILD due to nivolumab. Systemic steroid therapy promptly improved the patient's condition. Two months later, nivolumab has been able to suppress the tumor growth. Conclusion. Nivolumab may induce DILD soon after the first administration. However, despite these side effects, even a single administration of nivolumab can still effectively suppress tumor growth.