In the majority of patients lung cancer are only detected at advanced stages, they are mostly treated with chemotherapy or radiotherapy, or both, and the prognoses are usually poor. At present surgical resection is the only reliable curative method for the treatment of patients with lung cancer, and combined resection of the primary tumor and involved neighboring structures is performed when possible in patients with locally advanced disease. Tumors with direct extrapulmonary extension have been subdivided on the basis of the anatomic extent of disease and its potential for surgical treatment in the TNM classification for lung cancer: T3 lesions with limited, circumscribed extrapulmonary extension are considered potentially surgically resectable, whereas T4 tumors with extensive extrapulmonary extension are considered unresectable. Although surgical treatment for T3 lesions is generally accepted, the outcome is frequently not satisfactory. On the other hand, advanced surgical techniques are now being applied for T4 lesions due to the improvement of surgery and anesthesiology and progress in combined treatment modalities. This article reviews the results of surgical therapy for patients with lung cancer invading neighboring structures, including chest wall, superior sulcus, diaphragm, tracheal carina, left atrium, superior vena cava, aorta, and vertebrae. Furthermore, the surgical treatment of carcinomatous pleuritis is also assessed, and the role and future direction of surgical resection for locally advanced lung cancer is discussed.

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The WHO classification published in 1999 defines four major subtypes of pulmonary neuroendocrine tumor: typical carcinoid, atypical carcinoid, large cell neuroendocrine carcinoma, and small cell carcinoma. Although the clinicopathologic characteristics of each subtype (especially large cell neuroendocrine carcinoma) have been in dispute, some of them were recently clarified by a Japanese multicenter study. Accurate histopathologic diagnosis of these tumors requires correct recognition of neuroendocrine morphology, ancillary examinations such as immunohistochemistry, strict application of histopathologic criteria, and understanding of the clinicopathologic significance of each subtype. Diagnostic accuracy in distinguishing low-from high-grade tumors seems to be high, whereas it is low for differential diagnosis between large cell carcinoma and small cell carcinoma. Because the latter two subtypes also closely resemble one another in demographic and molecular aspects, their separation in the classification scheme will likely be discussed and reconsidered in the future. As large cell neuroendocrine carcinoma is known to have a poor prognosis after surgery alone, a standard adjuvant therapy should be established based on the accurate pathologic diagnosis of this subtype, not only postoperatively but also preoperatively.

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Objective. In the past, anti-neoplastic agents were thought to be ineffective for metastatic brain tumor because of the blood-brain barrier, therefore radiotherapy or surgery should be the first treatment of choice for brain metastases. Because magnetic resonance imaging (MRI) become commonly used in Japan, small brain metastases are detected frequently. Moreover, some newly developed anti-neoplastic agents are expected to be effective for brain metastases. The aim of this study was to evaluate the efficacy of recent chemotherapy regimens in patients with asymptomatic small brain metastases from non-small cell lung cancer (NSCLC). Patients and method. Between December 1998 and December 2004, 19 patients with asymptomatic small brain metastases from NSCLC received two or more cycles of chemotherapy in the International Medical Center of Japan Hospital. They were also assessable for extra-cranial and intracranial responses. The evaluation for intracranial responses was performed independently from the evaluation for extra-cranial responses after two cycles of chemotherapy. Survival and the causes of deaths were also examined. Results. Concerning the evaluation of intracranial responses, 2 of 19 patients had improvement. Fourteen patients had no change. As to the evaluation for extra-cranial responses, 3 patients achieved partial response and 11 had stable disease. During chemotherapy, no patient showed any neurological symptoms. Three patients finally died from meningeal carcinomatosis. Median survival was 10 months. Conclusion. There is the probability that recent chemotherapy has a certain effect on brain metastases and it may be useful for the first treatment in patients with NSCLC who have asymptomatic small brain metastases.

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Background. Skeletal muscle metastases from lung cancer are considered to be extremely rare. We encountered 3 cases of lung cancer associated with skeletal muscle metastases on initial medical examination or during disease progression. Cases. Case 1: A 46-year-old man was trismic due to metastasis of lung adenocarcinoma to the lateral pterygoid muscle. He was resistant to radiotherapy and chemotherapy, and died 9 months after the occurrence of symptoms. Case 2: A 57-year-old man had a large cell lung carcinoma or poorly differentiated lung adenocarcinoma. He had metastasis to the right femoral muscle in addition to multiple metastases to many other organs. His disease was also resistant to any treatment, and died 7 months after he became symptomatic. Case 3: A 64-year-old man with adenocarcinoma had a single metastasis to the biceps muscle. He died 3 months after the diagnosis of muscle metastasis due to resistance to therapy. Conclusion. Upon diagnosis of tumorous lesions of skeletal muscles, whole body examination and subsequent percutaneous biopsy of muscle involvement are required to determine the possibility of skeletal muscle metastasis of lung cancer.

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Objective. The clinical usefulness of FDG-PET in the diagnosis of lung cancer has been well established, however, false positive and negative cases are still sometimes reported. We therefore investigated the clinical usefulness of FDG-PET regarding distinguishing between benign or malignant solitary pulmonary nodules and lymph node metastases. Study Design. The subjects consisted of 37 consecutive cases (27 male, 10 female, mean age 66.7 years) of surgically resected thoracic tumors that had been scanned preoperatively by FDG-PET to define the presence of a benign or malignant, or to determine the clinical staging from March 2004 to July 2005. Primary lung cancers were noted in 33 cases while benign lesions were noted in 4 cases (1 sarcoid reaction, 1 sclerosing hemoinagioma, 1 fibrosis with hyperplasia, and 1 inflammatory lymph node). The operatiove procedures included 1 pneumonectomy, 30 lobectomies, 1 segmentectomy, and 5 partial resections. The pathological types of lung cancer included 18 adenocarcinomas, 9 squamous cell carcinomas, 2 large cell carcinomas, and 4 others. According to the pathological staging, 11 patients were stage IA, 8 stage IB, 3 stage IIB, 4 stage IIIA, 5 stage IIIB, and 2 stage IV. Results. Thirty-two and 5 nodules were positive and negative according to FDG-PET for the primary tumor, respectively. In lung cancers, 31 and 2 cases were positive and negative according to FDG-PET, respectively. In the benign lesions, 1 and 3 cases were positive and negative according to FDG-PET, respectively. The sensitivity and specificity of FDG-PET for detecting the primary tumor lesions were 93.9% and 75.0%, respectively. The 2 adenocarcinomas measuring less than 1 cm in size with a high percentage of ground glass opacity (Noguchi type B) were both false negative. The sensitivity and specificity of FDG-PET for detecting hilar lymph nodes was 100% and 85.2%, respectively. The sensitivity and specificity of FDG-PET for detecting mediastinal lymph nodes was 66.7% and 84.0%, respectively. Conclusion. The FDP-PET detection of main tumor limits for adenocarcinomas measuring less than 1 cm in size with a high percentage of ground glass opacity. On the other hand, there were cases of benign disease that show falsely positive results. We must use FDG-PET for the diagnosis of lung cancer based on a firm grasp of its merits and demerits.

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Background. Pleural fluid tests, such as cytodiagnosis, and thoracoscopy are useful in patients with retention of pleural fluid. Internists can perform thoracoscopy under local anesthesia, and observation and biopsy of lesions significantly increase the rate of diagnosis. Case. A 65-year-old woman had undergone surgery for right breast cancer at the age of 45. She was admitted for a detailed examination due to retention of pleural fluid in the left thoracic region. A pleural fluid test did not lead to a definitive diagnosis, so thoracoscopy was performed under local anesthesia. Recurrent breast cancer-related carcinomatous pleuritis was diagnosed. Conclusion. In this patient, thoracoscopy under local anesthesia diagnosed carcinomatous pleuritis. Case of recurrent breast cancer 20 years after surgery are very rare.

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Background. Emphysematous bullae are often associated with lung cancer. We report a case of asynchronous double lung cancers developing from the walls of bullae in the bilateral lungs. Case. A 50-year-old man underwent a right upper lobectomy for squamous cell carcinoma arising from the wall of a giant bulla 7 years ago. At the time, an emphysematous bulla was found in the left upper lobe. Follow-up chest X-ray showed abnormal shadow in the left upper lung field. Chest CT scan revealed beaded nodules along the wall of the bulla which contained slight fluid accumulation. The patient underwent a successful left upper lobectomy on a diagnosis of adenocarcinoma of the lung (pT2N0M0). Conclusion. Patients with emphysematous bullae need periodic follow-up because they are in the high risk group for lung cancer.

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Background. Anti-cancer agents often induce interstitial pneumonia, while interstitial pneumonia induced by uracil /tegafur (UFT) is very rare. We describe here a case of acute interstitial lung disease/diffuse alveolar damage due to UFT. Case. A 72-year-old man with squamous cell carcinoma of the lung underwent right lower lobectomy. We initiated UFT (300 mg/day) from day 33 after the operation. He complained of exertional dyspnea and progressive dry cough at 14 days after initiation of UFT. Four days later, he was urgently hospitalized because of progressive dyspnea, high fever and ground-glass opacity on his chest radiograph. He received mechanical ventilation and drug therapy including a steroid hormone. Without any improvement, however, he died at 48 days after rehospitalization. Drug-induced interstitial pneumonia caused by UFT was diagnosed, because only UFT was positive by drug lymphocyte stimulation test. Conclusion. Although adverse reactions to UFT are thought to be rare, we must observe patient carefully while administering it.

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Background. Pseudomesotheliomatous carcinoma of the lung (PMCL) is characterized by diffuse progression along visceral pleura, and has been confirmed histologically as a peripheral lung cancer. We report our experience of an autopsy case of PMCL. Case. A 71 year-old Japanese man presented with right chest pain and dyspnea in May 2003. A chest X ray film showed right massive pleural effusion. Adenocarcinoma was detected from pleural effusion and we diagnosed lung cancer (cT4N3M0 stage IIIB) by other detailed examinations. Although we attempted many different kinds of chemotherapies after insertion of a chest drainage tube in the right pleural space, he died 16 months after the diagnosis. At autopsy, no primary lesion was detected in the right lung, but the entire right lung was enclosed with thickened visceral pleura. Cancer tissue was detected along the pleura. Immunohistological examinations showed positive results for CEA and TTF-1, but negative for calretinin, so we finally diagnosed PMCL. Conclusion. We considered that not only cytological examination of pleural fluid but also histological examination is needed for a diagnosis of PMCL in a case of malignant pleural effusion when the primary lesion cannot be detected in the lungs.

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Background. Standard therapy for small cell lung cancer is considered to be chemoradiotherapy, and a role of surgery is limited. Case. A 44-year-old man was admitted with hemoptisis. Since small cell carcinoma of the lung in the right lower lobe was diagnosed, he underwent concurrent chemo-radiotherapy (cisplatin+etoposide+45 Gy) and additionally 3 courses of chemotherapy (cisplatin+etoposide+irinotecan). Diagnostic imaging indicated a complete response with images, but 20 months later, local recurrence was diagnosed. After 1 course of chemotherapy (cisplatin+irinotecan), complete response was achieved and he has underwent one more course of chemotherapy. Because the disease-free interval was 20 months and his recurrence seemed limited to the original site, he underwent salvage surgery (right middle and lower lobectomy). Viable cancer cells were confirmed in the resected specimen. He is alive without any recurrence four years after surgery. Conclusion. This case makes us reconsider the role of salvage surgery for recurrent small cell lung cancer.

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Background. Idiopathic thrombocytopenic purpura is a complication occurring rarely in patients with malignant tumors. Case. Stage IIIB squamous cell carcinoma of the lung was diagnosed in the left upper lobe of a 60-year-old man. He received three courses of chemotherapy (carboplatin and docetaxel) with concurrent thoracic radiation therapy. However, 28 days after the third course of chemotherapy, his platelet count decreased to 3,000/μ l and he suffered nasal hemorrhage. Simultaneously, multiple metastastic lesions was recognized is the brain and both lungs. In addition, based on the increase of PA-IgG level and findings of bone marrow paracentesis idiopathic thrombocytopenic purpura (ITP) was diagnosed. Although, he was given corticosteroids for the treatment of ITP, the platelet count did not increased. He died following a decline in physical condition. Conclusion. We report a case of lung cancer associated with ITP after concurrent chemoradiotherapy. This is considered to occur due to paraneoplastic syndrome because ITP appeared at the same time as tumor recurrence.

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Background. Metastatic adrenal tumors are frequently found at autopsy in patients with lung cancer. In recent years, metastases have been detected earlier because of the advances in diagnostic radiology. There have been an increase in reports that adrenalectomy improved the prognosis. However, there is no effective treatment for local recurrence after adrenalectomy. We encountered a long-term survivor who responded remarkably to treatment with uracil-tegafur (UFT). Case. A 71-year-old man underwent left lower lobectomy for lung cancer (adenocarcinoma, pT2N0M0 stage IB). Five months later, CT scan showed a right adrenal tumor. Adrenalectomy was performed, and a histopathological diagnosis of metastatic adrenal tumor was given. Local recurrence was noted 3 months later, with the tumor gradually invading upon the liver. UFT (300 mg/day) was administered, resulting in a reduction in the size of the tumor. Eight months later, the tumor had disappeared on CT. Three and a half years after the adrenalectomy, the patient is alive without further recurrence. Conclusion. These findings indicate the efficacy of UFT in a case of adrenal metastasis of non-small cell lung cancer.

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[in Japanese]

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[in Japanese]

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