Endoscopic laser treatment has been recognized as a lung-sparing local therapeutic modality that can achieve remarkable responses. In particular, photodynamic therapy (PDT) is able to obtain selective tumor necrosis safely and without unacceptable effects on surrounding tissue. PDT is a specific term that refers to the interaction of light with a photosensitizing agent in the presence of molecular oxygen, resulting in an oxygen-dependent photochemical process. The photosensitizing agent (e.g. Photofrin) absorbs photons of the appropriate wavelength (e.g. 630 nm), becomes an excited triplet species of the photosensitizer, and then transfers its energy to ground-state triplet oxygen to produce excited-state singlet oxygen. Singlet oxygen is a cytotoxic agent that produces cell death through interaction with cellular components. In Japan, PDT for the treatment of early hilar non-small cell lung cancer (stage 0 and I) was restricted to patients for whom the usual treatments for lung cancer were not appropriate, preservation of lung function was required, and in whom the distal tumor margin was clearly visible. We started fundamental studies of PDT in 1978, then applied it to clinical use. In 1980, the first PDT in the world for a patient with early hilar lung cancer was performed via bronchoscopy in our institute. By the end of 2003, the number of centrally located early stage lung cancer lesions treated curatively by PDT reached 221 lesions, and complete response (CR) rate was achieved in 84.6% (187 out of 221 lesions). According to retrospective analysis, curative treatment of early hilar lung carcinoma is possible using PDT alone when the tumor size is below 1 cm and the distant margin of the lesion is visible. Furthermore, the endoscopic evaluation before treatment seems to be a crucial factor in PDT. This paper reviews the experience of our institution; pre-treatment evaluation (autofluorescence diagnosis, EBUS), the art of PDT and results of clinical application. The expanding role of PDT in advanced lung cancer (e.g. palliative PDT, pre-operative PDT) is also discussed.

View full abstract

Data on new cytotoxic agents, pemetrexed and amrubicin, for lung cancer were reviewed. Pemetrexed was equally effective and less toxic than docetaxel in patients with previously treated non-small cell lung cancer. A clinical study of pemetrexed is now ongoing in Japan. In a phase II study of amrubicin for extensive disease small-cell lung cancer (ED-SCLC), the response rate was 76%. Since a combiantion of amrubicin and cisplatin was highly effective for ED-SCLC, a randomized study comparing this combination with irinotecan plus cisplatin is planned.

View full abstract

Objective. This study investigated the clinical aspects of surgically treated elderly patients with non-small cell lung cancer (NSCLC). Methods. A total of 726 patients including 102 elderly patients 75 or more years of age, who underwent surgery for NSCLC between April 1982 and December 1999 were retrospectively evaluated. Results. The percentage of patients who underwent limited operations or lymph node dissection of level 1 or less was significantly higher among elderly patients than among younger patients (3.5% vs 9.8%; p<0.01, 8.5% vs 20.6%; p<0.01, respectively). The ratios of patients with pathological stage III disease was significantly lower among elderly patients than among younger patients (23.2% vs 12.7%; p<0.05). Postoperative adjuvant therapies were perfomed for a lower percentage of elderly patients than younger patients (27.1% vs 11.8%; p<0.05). Preoperative and postoperative complications occurred in 57.8% and 40.2% of the elderly patients, respectively. The surgical mortality rate was 3.9% among elderly patients and 1.3% among younger patients, with only a marginal difference. The ratio of non-cancer related death was higher among elderly patients than among younger patients, especially in pathological stage I (27.0% vs 60.0%; p<0.05). The 5-year survival rate of the elderly patients with pathological stage I disease was 69.6% and significantly worse than that of younger patients in the same stage. The analysis of prognostic factors in the elderly group demonstrated that the pathological stage was the only significant factor on both univariate and multivariate analysis. Conclusion. The prognosis of elderly patients was acceptable whereas the percentage of non-cancer-related death was higher. Surgical treatment was considered an effective therapeutic method even in elderly patients.

View full abstract

Objective. Lung volume reduction surgery (LVRS) reportedly enables surgeons to perform pulmonary resection in case of lung cancer associated with emphysema and low pulmonary function, which do not comply with the conventional criteria for functional pulmonary resection. This study was performed to predict cases in which LVRS effects are attainable. Method. To assess predicted and measured residual pulmonary function after resection for lung cancer, the percentage of predicted residual pulmonary function and the percentage of measured residual pulmonary function (FVC and FEV_1.0) were compared by Student's paired t-test between the group of patients with pathologically normal lung tissue (61 patients) and the group of patients with concomitant emphysema (43 patients). Results. In the patients with normal lung tissue, the percentage of measured residual pulmonary function was not significantly different from the percentage of predicted residual pulmonary function (FVC and FEV_1.0). On the other hand, in the group of patients with emphysema, the percentage of measured residual pulmonary function was higher than the percentage of predicted residual pulmonary function (FEV_1.0, p = 0.0072). In the group of patients with emphysema, the percentage of measured residual pulmonary function was higher than the percentage of predicated residual pulmonary function (FVC and FEV_1.0) in 23 patients with matching resection site and area of low blood flow in the blood flow scintigram (FVC: p = 0.0042, FEV_1.0: p = 0.00014). Conclusion. Measured postoperative residual FEV_1.0 tends to be higher than predicted in patients with emphysema and it is assumed that LVRS effects are attained particularly in patients with lower blood flow at the resection site.

View full abstract

Objective. We investigated the mode of lymph node metastases and the validity of elective mediastinal lymph node dissection in patients with cancer of the upper lobes of the lung. Methods. Among patients with primary lung cancer resected in our hospital from 1986 to 2003, 44 patients with resected lung cancer located in upper lobes and pathological N2 disease after mediastinal and hilar lymph node dissection (ND2a) analyzed with regard to the mode of lymph node metastases. Results. Of 14 patients with lung cancer of right upper lobe, there were 12 patients with mediastinal superior region metastases and 4 patients with mediastinal inferior region metastases. Skip metastasis was seen in one patients, who had metastasis to the superior mediastinal region. There were no patients with skip metastasis to the inferior mediastinal region. With regard to 30 patients with lung cancer of the left upper lobe, among 22 patients with lung cancer of upper division of the left upper lobe, there were 21 patients with superior and aortic region mediastinal lymph node metastases and 2 patients with inferior region mediastinal lymph node metastases. Skip metastasis was seen in 9 patients, who all had aortic region mediastinal node metastases. Among 8 patients with lung cancer of the lingular division, there were 5 patients with superior and aortic mediastinal region lymph node metastases and 7 patients with inferior mediastinal region metastases. Skip metastasis was seen in one patient, who had multiple station mediastinal lymph node metastases to both the superior and inferior regions. Conclusion. According to the mode of lymph node metastases, mediastinal lymph node dissection of the inferior region can be omitted in patients with lung cancer of the right upper lobe or the upper division of the left upper lobe, if hilar and superior/aortic mediastinal lymph nodes have no metastases on the intraoperative frozen section.

View full abstract

Background. Bullous emphysema has been proven to be an important risk factor for lung cancer. Methods. Among 922 patients with lung cancer who underwent surgery at our institution from 1991 to 2004, a total of 6 patients with primary lung cancer arising from the walls of bullae were reviewed, in order to clarify the clinicopathological characteristics. Results. Chest CT revealed an irregular opacity on the wall of a bulla in 1 case, a thickened wall in 1 case, a tumor protruding into the bullae in 2 cases, and a tumor protruding into the lung parenchyma in 2 cases. The intervals between the discovery of bullae and the diagnosis of lung cancer was 71 months, 48 months, and 21 months in 3 cases, while in the remaining 3 cases the bullae and nodule were both found at the same time. A preoperative histological diagnosis of lung cancer was only documented in 1 case. Histologically, 5 cases were adenocarcinoma and one was a large cell neuroendocrine tumor. In the 5 cases of adenocarcinoma, 4 cases are alive without recurrence, while one case died from pneumonia without recurrence. The case with the large cell neuroendocrine tumor is still alive with recurrent disease. Conclusion. It is important to keep in mind the possible occurrence of lung cancer from the walls of bullae, therefore, a careful follow-up by CT is recommended for patients presenting with emphysematous bullae. When carcinoma is suspected, appropriate surgical procedures should be considered.

View full abstract

Background. ¹⁸F-fluorodeoxyglucose (FDG) positron emission tomography (PET) plays an important role in determining disease stage and evaluating response to treatment in cancer patients. However, there are few reports concerning the use of FDG PET for diagnosing postoperative recurrence of malignant tumors such as lung cancer. In a recent case, we found FDG PET to be useful for detecting postoperative metastasis of lung adenocarcinoma to the thoracic wall. Case. The patient was a 54-year-old woman who, in 2000, underwent right lower lobectomy with ND2 dissection to treat adenocarcinoma (pT2N0M0) in the superior segment (S⁶) of the right lung. Thirty-two months after surgery, the carcinoembryonic antigen level had risen to 21 ng/ml. Systemic examinations, including chest computed tomography, revealed neither recurrent tumor nor double cancer. However, FDG PET, performed 35 months after surgery, revealed accumulation of radioactivity in the right precordial region. Chest computed tomography and magnetic resonance imaging were performed, and thoracic wall metastasis was diagnosed on the basis of imaging findings. Thirty-eight months after the first surgery, the patient underwent resection of the right anterior thoracic wall. A disc-shaped tumor was found between the parietal pleura and the intercostal muscles, and blood-borne metastasis to the extra-pleural fatty tissue was diagnosed. Conclusion. FDG PET appears to be useful for detecting postoperative metastasis of non-small cell lung carcinoma.

View full abstract

We report a case of MALT lymphoma of the lung. Case. A 67-year-old woman was referred to our hospital because of atelectasis in the S³ of the right lung, which had not been improved during the previous 1 year. She had a past history of abnormal chest shadow of the right upper lung field 3 years previously. Chest computed tomography (CT) scanning showed an infiltrative shadow, spreading from the central to pleural region of the S³. The margin was sharp and there was an air bronchogram. The serum level of various tumor markers was within the normal range. Transbronchial biopsy specimen revealed mucosa-associated lymphoid tissue (MALT) lymphoma. Additional examinations including Ga scintigraphy showed no abnormal lesion except for the S³ lesion. She underwent right upper sleeve lobectomy with lymph-node dissection. Although the post-operative histopathologic examination suggested invasion at the bronchial stump, she did not receive adjuvant chemotherapy or additional radiation therapy. Conclusion. Surgery is considered to be a useful treatment for pulmonary MALT lymphoma of the localized type, based on previous several observations, however it has not been clarified whether complete resection is the most effective in terms of prognosis. Considering the difficulty in frozen section diagnosis, uncertain effect of chemotherapy or radiation therapy and invasion of extended damage due to radical resection, further examination is necessary to determine the best treatment.

View full abstract

Background. Primary malignant lymphoma developing from the chest wall is extremely rare and is generally believed to be closely related to preceding pleural disease such as chronic tuberculous pyothorax or EB virus infection, and is considered to have a poor prognosis. We encountered a case of non-Hodgkin's lymphoma (NHL) which developed from the right-side chest wall without any preceding pleural disease and which we successfully treated with surgery and adjuvant chemotherapy. Case. A 17-year-old adolescent boy consulted our hospital complaining of chest pain and right-sided chest wall swelling. Chest X-ray and computed tomography revealed a soft tissue mass 7 cm in diameter involving the fourth rib with osteolysis. On a percutaneous needle biopsy of the tumor, histological examination indicated the proliferation of atypical cell suspected to be a sarcoma, and en-bloc chest wall combined resection with the right 3-5th ribs was performed. A final diagnosis of large cell type, non-Hodgkin's B cell lymphoma was established. After postoperative chemotherapy (cyclophosphamide, doxorubisin, vincristine, predonisolon: CHOP), the patient is alive well, and there was no evidence of recurrence on his 5 year follow up examination. Conclusion. We report a rare case of primary malignant lymphoma developing from the chest wall without any preceding pleural disease in which surgery and adjuvant chemotherapy yielded a good outcome.

View full abstract

Background. Esophageal stenting has emerged as a common palliative treatment for esophageal stenosis due to malignant tumor. However, acute tracheo-brochial obstruction after esophageal self-expanding metallic stent (SEMS) placement is sometimes life-threatening and must be considered as an important adverse event. Recently cases of acute tracheo-bronchial obstruction after insertion of esophageal stents have been reported, and the use of tracheo-bronchial stents for treating adverse events has been a matter of recent contention. Case. We report the case of a 68-year-old man with lung cancer who underwent chemo- and radiotherapy. Esophageal stenosis developed due to relapse of mediastinal lymph node metastasis, and a SEMS was placed for esophageal stenosis. Acute bronchial obstruction induced by mediastinal lymph node migration occurred 18 h later. After SEMS placement for the bronchial obstruction, symptoms improved markedly. However he died of pneumonia due to esophago-tracheobroncheal fistula. Conclusion. When placement of SEMS is needed for malignant esophageal stenosis, prophylactic tracheo-bronchial stenting to avoid acute tracheo-bronchial obstruction should be discussed. Such cases must undergo strict follow-up until 4 weeks after esophageal SEMS placement. In addition, after placement of double stenting, the possibility of the development of esophago-tracheobronchial fistula must be carefully considered.

View full abstract

Background. We treated a case of pleomorphic carcinoma with rapid growth in the right upper lobe of the lung. The clinicopathological characteristics are reported. Case. A 66-year-old man presented with a tumor shadow detected on follow-up CT scan after an operation for gastric cancer. A definitive diagnosis was not obtained by transbronchial lung biopsy, however primary lung cancer was highly suspected based on the CT findings. The tumor rapidly enlarged from 2 cm to 7 cm in 2.5 months. The only metastasis suspected was on the metaphysis of the left femur by bone scintigraphy, plain X-ray and MRI examinations. Right upper lobectomy was performed, considering the necessity of local control. The final diagnosis of pleomorphic carcinoma was a result of the pathological examination of the resected specimen. Brain metastasis occurred five months after the operation and radiation therapy was performed. However, surgical resection of the brain tumor was performed eight months after the radiation therapy because the response was temporary. Presently, no local recurrence of primary lesion and no change in the state of the left femur are noted. Conclusion. Careful considerations are needed to decide the operability of pleomorphic carcinoma cases because of a high-grade malignancy characteristic. The surgical resection for primary or metastatic lesions must be one of the useful treatments for local control and palliative therapy for patient's symptoms.

View full abstract

Background. In 1991, Travis et al. proposed a new category of large cell neuroendocrine carcinoma (LCNEC). Some investigators reported poor prognosis of LCNEC patients, with 5-year survival rates similar to small cell carcinoma. We report a case of LCNEC with aggressive progression after complete resection. Case. A 71-year-old man underwent left pneumonectomy and lymph node dissection for lung cancer on June 13, 2002. No finding suggested distant metastasis. The pathological diagnosis was large cell neuroendocrine carcinoma, T2N1M0, stage IIB. Two months after surgery, he presented with lumbago. Bone scintigram and magnetic resonance imaging revealed bone metastasis to the right sacroiliac joint. A brain metastasis was also detected by computed tomography. He received 30-Gy brain irradiation and 30-Gy bone radiotherapy to relieve the pain. Although the radiotherapy alleviated the pain, the brain and sacroiliac joint metastases did not shrink. The patient died of recurrent lung cancer 99 days after the surgical resection. Conclusion. We reported an aggressive progression case of pulmonary LCNEC. Prognosis and treatment efficacy in LCNEC patients remain controversial, and further investigation is needed.

View full abstract

Background. “Pleomorphic carcinoma” in the new World Health Organization (WHO) classification of lung and pleural tumours is a problematic category of mixed different contents. Case. A 74-year-old man was pointed out to have a cavitary mass shadow in the right upper lung field in a routine health check carried out one year previously. The shadow had enlarged over the following year and bronchoscopic cytology revealed Class V, non-small cell carcinoma cells. Right upper lobectomy and lymph node dissection (ND2a) were performed. A mass lesion located in the right S¹ measured 2.5 cm in greatest dimension and had hemorrhagic infarction in the peripheral lung. The histological features were challenging, with numerous mitotic figures in pleomorphic spindle cells and remarkable admixture of various inflammatory reactions. Immunohistochemistry revealed that most atypical cells were positive for epithelial membrane antigen (EMA), minimally positive for cytokeratin (AE1/AE3) and negative for carcinoembryonic antigen (CEA). After a consultation with the Armed Forces Institute of Pathology (AFIP), the final diagnosis of pleomorphic carcinoma predominated by spindle cell component was obtained. Six months after the operation, the carcinoma metastasized to the lumbar and sacral vertebrae, and two more months later the patient died of brain metastasis. Conclusion. By presenting a rare case of pleomorphic carcinoma of the lung with a predominant spindle cell component and giant cells, the authors suggest that strong cellular atypia and predominance (e.g. 50% or more) of the sarcomatoid component should be fully considered for the definition of “Pleomorphic carcinoma”.

View full abstract