Objective. To promote an understanding of home palliative care, and to demonstrate that it is the most appropriate choice for treatment in the terminal stage of cancer, especially lung cancer. Method. We analyzed the following factors related to care quality in 553 patients who received home palliative care: 1) mortality at home, 2) maintenance of walking ability, as an ADL-related factor, 3) communication using spoken language, 4) maximum narcotic dose and change in dose at end of life, as an assessment of the alleviation of suffering (e.g., pain, dyspnea). Results. 1) Mortality at home was 96.1% overall (lung cancer: 96.3%, non-lung cancer: 96.1%). 2) Examination of walking ability in patients who had been able to walk on their own at the start of home care revealed that, overall, 46.4% and 32.6% of the patients had gone to the bathroom, albeit with assistance, 2 days before death and on the day before death, respectively (lung cancer: 45.2% and 35.5%, respectively; non-lung cancer: 46.9% and 31.5%, respectively). 3) Examination of communication in patients who had been able to talk at the start of home care revealed that, overall, 87.3% and 75.7% of the patients were capable of communicating using spoken language 2 days before death and on the day before death, respectively (lung cancer: 86.0%, and 76.9%, respectively; non-lung cancer: 87.8% and 75.2%, respectively). 4) 165 of the patients, or 34.9%, did not use narcotics to alleviate their suffering, and the symptoms of most of those who used narcotics were alleviated by 200 mg/day or less of oral morphine equivalents. Moreover, the doses were not increased at the end of life in most of the patients. Conclusion. It was demonstrated that terminally ill cancer patients can be cared for at home until they die, and that the quality of care received at home is high. Home palliative care should therefore be actively promoted as the preferred method of care in terminal-stage cancer patients.

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Many drugs have adverse reaction, especially in palliative medicine due to pharmacological changes induced in advanced cancer patients caused by such situation as decreased renal function. In particular, patients with terminal illness often have so many symptoms that it is difficult to identify the cause of each of them. Patients with advanced cancer experience nausea, vomiting, and delirium in addition to pain. Nausea and vomiting are caused by hypercalcemia, intracranial hypertension, constipation, digestive organ confinement and medicines characteristics such as opioids or the selective serotonin reuptake inhibitors (SSRI). The strategy for nausea and vomiting varies with the cause. Therefore, it is necessary to carefully analyze the causes. Drug information is the one of the important roles of pharmacists in palliative care. This report describes how, as a pharmacist, investigate causes and the strategies to be used for nausea/vomiting, delirium, and anxiety.

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Today most people fall into a deep sleep and never wake up in hospitals, where they are supposed to receive medical supports, instead of dying in their familiar and beloved home. Even those who choose facilities, such as nursing homes etc, as their last home, may have to move into hospitals before death for several days or even a few hours. Consequently, these terminal care is handled by only the hospital personnel with heavy responsibilities. As medical advances shorten hospital stays the site of death will more be the home. For those who want to go home at the end of their life, there will be more social supports and facilities in their community.

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Dyspnea (defined as "an uncomfortable sensation of breathing") is one of the most frequent and refractory symptoms of lung cancer patients. Dyspnea decreases the quality of life of both patients and their families. If also affects their treatment process and even prognosis. Therefore it is very important to evaluate and manage dyspnea appropriately. To treat the underlying causes (e.g. drainage of pleural effusion etc.) is the first line. However, the underlying causes are often irreversible and untreatable. It is important to estimate life expectancy by using the Palliative Prognostic Index. It was confirmed that morphine alleviates dyspnea. Anxiolytics and corticosteroids also alleviate dyspnea in some cases. Since dyspnea in cancer patients has multidimensional aspects, an interdisciplinary team approach for the symptom management is important.

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Objective. Respiratory exposure to asbestos has been associated with mesothelioma in humans. However, its carcinogenic mechanism is still unclear. Methods. Here we studied the ability of chrysotile, crocidolite and amosite fibers to induce oxidative DNA damage and the modifying factors using 4 distinct approaches. Results. Electron spin resonance analyses showed that crocidolite and amosite containing high amounts of iron, but not chrysotile, catalyzed hydroxyl radical formation in the presence of hydrogen peroxide, which was enhanced by an iron chelator, nitrilotriacetic acid, and suppressed by Desferal^®. Iron chelators, such as citrate, ATP and GTP, did not inhibit this reaction. Second, we used time-lapse videomicroscopy to evaluate how cells deal with asbestos fibers. RAW264.7 cells, MeT-5A and HeLa cells engulfed asbestos fibers, which reached not only cytoplasm but also the nucleus. Third, we utilized supercoiled plasmid DNA to evaluate the ability of each type of asbestos to induce DNA double strand breaks (DSBs). Crocidolite and amosite, but not chrysotile, induced DNA DSBs in the presence of iron chelators. We cloned the fragments to identify break ends. DSBs tended to occur within repeat sequences and between two G: C sequences. Finally, intraperitoneal administration of each type of asbestos to rats induced not only formation of nuclear 8-hydroxy-2'-deoxyguanosine in the mesothelium but also significant iron deposits in the spleen. Conclusion. Together with the established carcinogenicity of intraperitoneal chrysotile, our data suggest that asbestos-associated catalytic iron, whether constitutional or induced by other mechanisms, plays a role in asbestos-induced carcinogenesis and that chemoprevention may be possible through targeting the catalytic iron.

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Objective. It has been reported that serum osteopontin (OPN) levels of persons with exposure to asbestos who have malignant pleural mesothelioma (MPM) are increasing and useful for early diagnosis of MPM. OPN contains binding sites for several receptors including αvβ3 integrins, which are thought to play various roles in mediating cell-matrix interactions. The aim of this study is to evaluate roles of OPN in MPM cell line. Methods. With MPM cell lines, we conducted reverse transcriptase-polymerase chain reaction (RT-PCR) to evaluate OPN mRNA expression. Expression of integrins on the surface of this cell line were analyzed with a FACScan^TM. To evaluate cell adhesion and proliferation mediated by OPN, cells were added to 96-well flat bottom plates coated with OPN, bovine serum albumin (BSA), poly-L-lysine (PLL) or hyaluronate (HA). Adherent and viable cells were counted with cell counting kit-8^TM. To evaluate phosphorylation of focal adhesion kinase (FAK) in H28 cells on OPN, we performed immunoprecipitation and immunoblotting. Apoptotic cells cultured on these plates were detected by the binding of annexin V. Results. OPN and αvβ3 expression was detected with both RT-PCR and FACScan^TM, respectively. H28 cells adhered to OPN, PLL, or HA to much greater extent than to BSA. However, H28 cells cultured on OPN coated plates showed enhanced proliferation, but not on BSA, PLL or HA. In addition, high level of phosphorylated FAK in H28 cells plated on OPN was observed. Furthermore, less apoptotic cells were revealed cultured on OPN coated plates in comparison to others. Conclusion. In conclusion, OPN may play an important role in the enhancement of adhesion and proliferation of H28 cells, presumably by interacting with αvβ3 integrins.

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Objectives. Differential diagnosis of pleural mesothelioma in the early stage and reactive mesothelial hyperplasia is important to determine therapeutic strategy, but the morphological discrimination between them is very difficult. It has been reported that the p16^INK4A and NF2 genes are frequently deleted in malignant pleural mesothelioma in the advanced stage. In this study, we examined whether these gene abnormalities are useful to discriminate between pleural mesothelioma in the early stage and reactive mesothelial hyperplasia. Method. Cases of malignant pleural mesothelioma in the advanced stage (16), pleural mesothelioma in the early stage (2), and reactive mesothelial hyperplasia (3) were selected based on morphological and immunohistochemical examinations and their tissues were analyzed for the p16^INK4A and NF2 genes by real-time PCR. Results. The p16^INK4A gene was deleted in all cases (16/16) and the NF2 gene was deleted in most cases (15/16) of advanced stage malignant pleural mesothelioma, whereas all cases (3/3) of reactive mesothelial hyperplasia retained these genes. As for early stage pleural mesothelioma, the p16^INK4A gene was deleted in both cases (2/2), one of which (1/2) showed the deletion of the NF2 gene. Conclusion. The gene diagnosis of p16^INK4A and NF2 locus may be useful for the discrimination of early stage pleural mesothelioma and reactive mesothelial hyperplasia.

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Malignant pleural mesothelioma (MPM) is a highly aggressive, incurable neoplasm associated with asbestos exposure. It is estimated that the incidence of this disease will continue to increase until at least the year 2030 in Japan. There is some evidence that patients with MPM respond better to treatment if it is delivered early in the disease. A few MPM biomarkers have been reported, but until recently, no reliable serum marker to help the diagnosis of MPM or to predict response to treatment or prognosis, had been identified. Therefore, we performed a prospective, multicenter study to evaluate the significance of soluble mesothelin-related peptides (SMRP) as a biomarker for diagnosis of MPM. In this paper, we review the key advances in the understanding, treatment, and a biomarker for the diagnosis of MPM. Furthermore, we report some results of a prospective, multicenter study.

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The incidence of mesothelioma is expected to increase dramatically over the next few decades. Survival of patients with mesothelioma is very poor, regardless of recent advances in chemotherapeutic modalities that combine cisplatin and the new antifolate, pemetrexed. New strategies based on better understanding of the biology of the disease are thus clearly needed to improve the treatment efficacy of this fatal disease. In this study, anti-tumor effect of amrubicin was examined by the colorimetric cell proliferation assay, and dose-dependent inhibition of the proliferation was observed in mesothelioma cell lines. In addition, the combination of cisplatin with amrubicin was more effective than that of cisplatin with pemetrexed. Furthermore, the adjunct use of a cyclooxygenase 2 inhibitor, celecoxib was shown to significantly enhance treatment efficacy of the combination of cisplatin and pemetrexed. These findings suggest that a cyclooxygenase 2 inhibitor may be promising in the treatment of mesothelioma, especially because of its enhancement of the treatment efficacy of conventional anticancer agents without compromising quality of life.

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Objective. The clinical significance of multimodality therapy including surgery for malignant pleural mesothelioma (MPM) has not been established, due to the lack of clinical evidence of its benefit as well as concern regarding its higher toxicity. Method. A total of 19 consecutive patients with MPM, who underwent surgery for curative intent at our institution from April 2004 through November 2007, were retrospectively reviewed. Results. Extrapleural pneumonectomy (EPP) was completed in 16 (84%) patients, and pathological complete resection was achieved in 14 (74%) patients. In 81% of patients, preoperative clinical stage was lower than postoperative pathological staging, suggesting that the degree of tumor progression is often underestimated preoperatively. Fatal postoperative complications developed in 2 of 14 patients who underwent EPP, and one patient died of adult respiratory distress syndrome 42 days after EPP. Conclusion. Future clinical trials should be conducted to assess clinical benefit of multimodality therapy, including EPP, for MPM with careful patient selection and proper perioperative care.

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Malignant pleural mesothelioma (MPM) is a highly lethal and refractory malignancy caused by asbestos exposure. As local treatment, such as surgical resection or radiotherapy, is of limited efficacy, systemic chemotherapy plays an important role in improvement of treatment outcome. The results obtained from a large-scale phase III study led to approval of pemetrexed, a novel antifolate, by the U.S. Food and Drug Administration (FDA) as the world's first therapeutic agent for MPM, and combination treatment with pemetrexed plus cisplatin has been recognized as standard chemotherapy for this disease in the first-line setting. Recent studies provide evidence that second-line chemotherapy for malignancies including MPM, is closely related to prolonged survival. To date, however, no chemotherapeutic regimens have been recommended in the second-line setting for MPM. To evaluate the efficacy and safety of combination chemotherapy with pemetrexed plus cisplatin in the second-line setting for unresectable MPM, a prospective multi-institutional study, as a project of the "Comprehensive approach on asbestos-related diseases" supported by the "Special Coordination Funds for Promoting Science and Technology", has been commenced in Japan.

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Objective. Multimodality therapy is essential to improve surgical outcomes of potentially resectable malignant pleural mesothelioma (MPM), but optimal treatment has not yet been established. To assess compliance and safety of a multimodality therapy consisting of preoperative chemotherapy, surgery and postoperative radiation, a prospective clinical study is planned. Method. We conducted this prospective study as a project of the "Comprehensive approach of asbestos-related diseases" supported by the "Special Coordination Fund for Promoting Science and Technology of the MEXT of Japan". Results. A multi-institutional feasibility study was approved and is now ongoing. Eligible patients will be treated with 3 cycles of chemotherapy using cisplatin and pemetrexed, followed by extrapleural pneumonectomy and postoperative hemithoracic radiation. Primary endpoints are the rate of complete resection and the mortality rate. The expected number of eligible patients participating in the study is 40 during the next 3 years. Conclusion. When this study is completed and the feasibility of multimodality treatment for resectable MPM is confirmed, a phase II study to assess the efficacy may be planned.

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Objective. Intensive research has been conducted to identify factors associated with favorable clinical outcomes of gefitinib-treated patients with non-small-cell lung cancer. Epidermal growth factor receptor (EGFR) mutations have been reported as a predictive factor for favorable prognosis of gefitinib-treated patients with lung adenocarcinoma. However, its confounding with sex and smoking makes EGFR mutations' unique effect on patient survival. In this study, we analyzed a large-scale database to determine the survival impact of EGFR mutation against those of sex and smoking after gefitinib therapy. Materials and Methods. EGFR mutations in exon19 and exon21 defined as drug-sensitive EGFR mutations were examined to investigate the impact of EGFR mutation, sex, and smoking status on survival of 362 gefitinib-treated patients with lung adenocarcinoma. Results. Drug-sensitive EGFR mutations were detected in 169 patients (46.7%). The multivariate analysis including EGFR, sex and smoking status showed that drug-sensitive EGFR mutations were significantly related to prolonged overall survival (OS)(Hazard ratio=0.48, 95% confidence interval=0.36-0.63, P<0.001)(PFS: Hazard ratio, 0.29, 95% confidence interval=0.22-0.37, P<0.001) and progression-free survival (PFS)(P<0.001). In addition, we investigated 1) the impact of sex and smoking status according to EGFR status and 2) the impact of EGFR status according to sex and smoking status on survival. Sex and smoking status were not significantly associated with prolonged OS and PFS according to EGFR status. Drug-sensitive EGFR mutations were significantly associated with prolonged OS and PFS according to sex or smoking status. Conclusion. Our results indicated that drug-sensitive EGFR mutations were the only factor for prolonged survival of patients treated with gefitinib, suggesting that patient selection based on EGFR status for gefitinib therapy will lead to better understanding the effect of gefitinib as well as a better outcome for patients with lung adenocarcinoma.

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Objective. The Wnt and EGFR signaling pathways play crucial roles in the pathogenesis of a variety of malignant tumors. While the details of each cascade are understood, very little is known about their collective effects in non-small cell lung cancer (NSCLC). Methods. A total of 238 NSCLC samples were examined for methylation of Wnt antagonists (sFRP-1, sFRP-2, sFRP-5, Wif-1, Dkk-3) and for EGFR and KRAS mutations. Protein expression levels of β-catenin were assayed in 91 of the 238 NSCLCs. Results. We found that (a) aberrant methylation of Wnt antagonists is common in NSCLCs; (b) methylation of sFRP-2 is more prevalent in females, non-smokers, and adenocarcinoma cases; (c) there is a positive correlation between activated EGFR mutation and nuclear accumulation of β-catenin; (d) KRAS mutation and aberrant methylation of Wnt antagonists are positively correlated; and (e) EGFR mutation is significantly associated with a good prognosis in tumors lacking methylated Wnt antagonist genes. Conclusion. These results contribute to a better understanding of the cross-talk between the Wnt and EGFR signaling pathways, and help foster development of chemotherapeutic treatments in NSCLCs.

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The Wnt signal pathway is involved in embryogenesis, differentiation, and tumorigenesis. We have found that Wnt overexpression frequently occurs to promote carcinogenesis in non-small cell lung cancer (NSCLC). First, we found that the transduction of MRP-1/CD9 gene into human cancer cells can induce the downregulation of Wnt1, Wnt2b, Wnt5a, and several Wnt targets. Clinical studies found that 89% of NSCLCs had overexpressions of Wnt1, Wnt2 or Wnt5a. The Wnt1-positive carcinomas had positive intratumoral expressions of c-Myc, Cyclin D1, VEGF-A, and MMP-7, and the high tumor proliferation index. The Wnt2-positive carcinomas also had positive intratumoral expressions of VEGF-A and high tumor proliferation index. On the other hand, an overexpression of Wnt5a was associated with stromal VEGF-A expression through a tumor-stromal interaction, to increase the tumor proliferation rate. Furthermore, overexpressions of Wnt1 and Wnt5a were independent prognostic factors for NSCLC patients. From these results, these Wnt members can be candidates for molecular-target therapy for NSCLC. We are performing experimental studies on Wnt-inhibiting gene therapy using adenoviral vectors expressing shRNA.

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Proteomic analysis is a comprehensive analysis of proteins. Recent advances in this field enable its application to clinical samples including surgically resected specimens and body fluids. In clinical applications its main techniques consist of 2-dimensional polyacrylamide gel electrophoresis (2-DE) and mass spectrometry (MS). Using 2-DE and surgically resected lung cancer specimens we identified napsin A, which was specific for primary lung adenocarcinoma, and reticulocalbin, which was related to resistance to platinum-based adjuvant chemotherapy. Furthermore, using MS we attempted to explore biomarkers for the selection of postoperative adjuvant chemotherapy with uracil-tegafur (PAC), and clarified that patients with no expression of either vimentin or myosin IIA showed a significantly better outcome, regardless of PAC. Though we hope that proteomic technology will contribute to the establishment of both a new screening method for the early detection and individualized therapy of lung cancer, several technical issues for the investigation of clinical samples have not yet been resolved. The main issues concern the dynamic range for analysis of clinical samples. It is important that the purpose of the proteomic analysis is clarified, and appropriate sample preparation suited for the purpose is essential.

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Objectives. Clinical pathways have become more common in clinical practice in Japan to improve costeffectiveness, allocation, and timing of medical services. Our clinical pathway for thoracotomy is applied in Japanese standard medical practice for surgery in patients with lung cancer. This study was designed to validate the appropriateness of our standard pathway for thoracotomy and to estimate the profit and loss situation in the Diagnosis Procedure Combination (DPC) payroll system of the Japanese Health Insurance system. Methods and Results. From November 2005 through August 2007, chest surgery was performed in 448 patients. Our clinical pathway was applied in 94.4% of these patients; 7.3% patients dropped out because of variance. The average hospital stay was 8.7 days in the patients who did not drop from pathway. The re-admission rate within 1 month after discharge was 0.8%. The mean number of variances was 1.6. Patient-related variance was most frequent (cardiovascular related, 31.5%; pain-related, 30.0%). During the study, we shortened the duration of treatment with antibiotics according to the CDC guidelines as recommended by the Japanese Surgical Society (3 days to 1 day). This did not increase the rate of surgical-site infections (0.9% to 1.1%, p>0.99). The profit and loss situation with the DPC payroll system was not inferior to that of the previous Japanese medical payment system (fee for service reimbursement, 1,212,150 yen with DPC, 1,176,910 yen with the previous system). Conclusion. Our clinical pathway for thoracotomy is rational and adequate. Implementation of the DPC system has not lead to any financial disadvantage.

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Background. We report a case of thymoma with squamous differentiation associated with lung cancer. Case. An 81-year-old man consulted his family doctor with chief complaints of shortness of breath and chest pain. A nodular shadow was noted in the left middle lung field of his chest X-ray, and the patient was referred to our Department of Respiratory Medicine. Transbronchial aspiration cytology was performed in the left B⁸a, and the tumor was diagnosed as adenocarcinoma. He was then referred to our department for surgery. The preoperative diagnosis of the lung cancer was classified as cT1N0M0 and stage IA by preoperative evaluation. Another 5.0×3.5 cm tumor was detected in the anterior mediastinum in the preoperative chest CT, and a thymoma was suspected. Simultaneous left lower lobectomy with lymphadenectomy (ND2a) and surgical removal of the anterior mediastinal tumor were performed. The postoperative histological examination revealed the lung cancer to be adenocarcinoma, pT2N0M0 and stage IB. The anterior mediastinal tumor was type B1 thymoma, showing squamous differentiation with keratinization. Conclusion. Thymoma with squamous differentiation is a rare histopathological feature. This case was valuable in that it suggested a relationship between thymoma and thymic carcinoma.

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Background. Benign metastasizing leiomyoma (BML) is a rare disease among the benign leiomyomas occurring in the lung. All of the cases had previously uterine leiomyoma, which was histologically benign. We present a case of BML complicating primary lung cancer. Case. A 51-year-old woman had undergone total abdominal hysterectomy under the diagnosis of uterine leiomyoma at the age of 38 years. She was found to have an abnormal shadow on chest X-ray, and was then referred to our hospital. Chest CT scan revealed an ill-defined solid tumor, which measured 1.9×1.8 cm in size and was located in the left S¹⁰, and a total of 19 smoothly marginated nodules, 3 to 7 mm in diameter, were also found in the bilateral lung fields. We performed thoracoscopic-assisted lower lung partial resections in order to make a definitive diagnosis and for treatment strategy decision. The tumor in the left S¹⁰ was a primary lung adenocarcinoma, while the small nodular lesions were determined to be BML. We subsequently performed left lower lobectomy and lymph node dissection for radical treatment of lung cancer. No additional therapy was done and, the patient remains asymptomatic without new growth of the lung tumors nor recurrence of the lung cancer 12 months after the lobectomy. Conclusion. To date, there are 123 cases of BML in the literature. This is the first case report of primary lung cancer complicating BML.

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Background. While the coexistence of sarcoidosis and lung cancer is unusual, when such case is encountered, there is a possibility that appropriate treatment for lung cancer is not selected because of overestimation of mediastinal lymphadenopathy. Case. A 60-year-old woman was admitted for evaluation of abnormal shadow on chest imaging studies. Chest computed tomography revealed a mass (23 mm) in the right lung (S²) and pretracheal (#3) lymphadenopathy of minor axis 11 mm. The mass was diagnosed as adenocarcinoma of the lung by transbronchial washing and brushing cytology. The preoperative diagnosis was clinical stage IIIA (T1N2M0) adenocarcinoma of the lung. Right upper lobectomy and mediastinal lymph node dissection (ND2a) was performed. Pathological findings revealed non-caseating granulomas in both most of the lymph nodes and the resected lung without any lymph node metastasis. Conclusion. We reported a p-stage IA (T1N0M0) adenocarcinoma of the lung with sarcoidosis. We must endeavour never to overlook a resectable case of lung cancer.

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Background. Although round atelectasis is a benign disease related to pleural plaque and benign asbestos pleural effusion, it sometimes requires differentiation from lung cancer. Case. A 59-year-old man with occupational exposure to asbestos for 11 years, was referred to us because of a growing pulmonary mass in the left lower lobe on chest computed tomography. Transbronchial lung biopsy and brushing cytology did not disclose any evidence of malignancy. Although round atelectasis was most suspected, malignant disease including lung cancer could not be excluded because of slight increasing in the tumor markers SLX and NSE. Thus, we performed wedge resection of the left lower lobe. The histopathological findings of the resected specimen showed thickened visceral pleura and chronic pleurisy. There was no evidence of malignancy. We finally established a diagnosis of round atelectasis. Conclusion. We reported a case of enlarging round atelectasis requiring differentiation from lung cancer.

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Background. The prognosis for leptomeningeal carcinomatosis from non-small-cell lung cancer (NSCLC) is poor. The median survival of patients without treatment has been reported to be approximately 4-6 weeks. Cases. We report 3 patients with leptomeningeal carcinomatosis resulting from lung adenocarcinoma: a 58-year-old woman, a 72-year-old man, and a 68-year-old woman with focal neurological dysfunction. Magnetic resonance imaging (MRI) of the brains of these patients revealed leptomeningeal dissemination. The cytology of cerebrospinal fluids (CSF) was positive for malignancy. They responded to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs). MRI imaging, and their CSF cytology as well as their neurological signs improved. Their survival time from the onset of leptomeningeal carcinomatosis was 6-14 months. EGFR mutations in the CSF were detected in 2 cases. Detection of EGFR mutations might be useful for predicting response to EGFR-TKIs in patients with NSCLC with leptomeningeal carcinomatosis. Conclusion. EGFR-TKIs are attractive treatment options for EGFR mutation-positive NSCLC with leptomeningeal carcinomatosis.

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Background. Paragangliomas are neuroendocrine tumors originating from the paraganglia apart from the adrenal medulla. Most originate from the paraganglia in the head and neck, retroperitoneum, and bladder, and few cases of primary lung paraganglioma have been reported. Case. A 58-year-old woman undergoing tests for thyroid cancer was found to have a nodular shadow at S¹⁺² of the left lung. We suspected the nodule to be a hamartoma of the lung, and she was monitored carefully over the next 2 years, during which time the nodule grew only slightly. Finally, we resected the nodule and the intraoperative pathological diagnosis was undifferentiated carcinoma; thus, we could not judge whether the tumor was a metastasis of thyroid cancer or a primary lung cancer. We decided we needed permanent specimens to establish a final diagnosis. So, we finished the operation. Histopathological examination revealed that the tumor consisted of cells with small nuclei, neurofilaments between the cells, and a widespread Zellballen pattern. Immunostaining revealed that the tumor stained positively with S-100, synaptophysin, NSE, and chromogranin A. According to these results, we diagnosed primary lung paraganglioma. The patient had an uneventful postoperative course and there have been no signs of recurrence or metastasis. Conclusion. We encountered a case of resection for primary lung paraganglioma. This is a very rare case, so we make a report with some reference to the literature.

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Background. Reports of right upper and lower lobectomy with preservation of the middle lobe are rare. Case. Abnormal shadows on chest X-ray film were found in an 89-year-old man on a medical examination. Chest CT scan revealed an irregularly shaped mass in the right lower lobe and a trabecular shadow in the right upper lobe. Bronchoscopy revealed the tumor in the right lower lobe bronchus. The biopsy of the tumor yielded a diagnosis of squamous cell carcinoma. The trabecular shadow of the upper lobe was suspected to be an inflammation. Video-assisted right lower lobectomy with lymph node dissection was performed. Postoperative pathological staging was pT1N2M0 p0d0E0pm0 stage IIIA. Nine months after the operation, he had lumbago, and ¹⁸F-fluorodeoxyglucose (FDG)-PET and CT were performed. On the thoracic CT, the shadow of the right upper lobe was enlarged. The standardized uptake value (SUV) of the lesion was 2.92, and lung cancer was suspected. Right upper lobectomy should be performed by postero-lateral thoracotomy. Adhesion of the middle lobe to the chest wall was not dissected to prevent the postoperative middle lobe torsion. Pathological findings of the resected specimen revealed adenocarcinoma of pT2N0M0, stage IB. Atelectasis of the middle lobe due to sputum was a postoperative complication, and aspiration via the bronchoscope was needed 3 times. Thirty months after the operation, he is alive without recurrence of the cancer. On the chest X-ray film and CT, the middle lobe has no emphysematous change, and he has only mild deformity of the thorax and mediastinal deviation. On perfusion scintigraphy, the middle lobe shows 12% of residual respiratory function. Conclusion. The operation of right upper lobectomy after the right lower lobectomy with preservation of the middle lobe is possible. The middle lobe is thought to have function and is worth preserving.

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Screening for a cancer should be considered when the cancer is significant in terms of incidence and mortality, treatment of early stage disease is better than treatment of late stage disease, and there is a screening regimen that provides for earlier diagnosis rather than later, symptom-prompted diagnosis. Lung cancer qualifies as it kills more people than any other cancer worldwide. In the United States it kills more people than colon, breast, and prostate cancer combined and more women than breast cancer. The fundamental concepts of screening are presented. Screening for a cancer is a repetitive process, starting with the baseline round followed by repeat rounds of screening at set intervals. The regimen of screening defines the initial diagnostic test and the sequence of tests to be performed leading to a rule-in diagnosis of the cancer. The regimen should provide lead time of the diagnosis of the cancer. The regimen for the first, baseline round may be different from the regimen for the repeat rounds as the former is inherently different from the subsequent repeat rounds. Baseline screening identifies a greater proportion of cancers with a longer latent (asymptomatic) phase than repeat screening, called length bias. Length bias exists for any screening program, regardless of the design of the study or the cancer. Repeat rounds of screening identify the same proportion of cancer diagnoses found in absence of screening for people having the same risk of the cancer and these repeat rounds of screening can be pooled. It is also a consequence of length bias that cancers found in repeat rounds are earlier in their latent phase than those of the baseline round, a less frequently mentioned consequence. Overdiagnosis bias, another bias of screening, can occur in two ways: 1) a 'cancer' detected by the screening, pathologically proven, that is not life-threatening even when not resected and 2) a genuine life-threatening cancer that is diagnosed and treated but the person dies of another disease or accident. This bias can be addressed in various ways, including by the regimen of screening and by following those who refuse treatment. As screening is pursuit of early diagnosis followed by early treatment, both the diagnostic and treatment performance can be addressed separately. Key diagnostic performance measures of the regimen are: 1) the proportion of screen-diagnoses among all diagnoses and 2) the stage distribution of the diagnosed cancers. These performance measures are unaffected by the frequency of lung-cancer diagnoses and thus also unaffected by the enrollment criteria. The key prognostic performance measure is the curability rate which is provided by the long-term follow-up of all diagnosed cases of lung cancer, regardless of stage and treatment. It can also be estimated by the proportion in Stage I multiplied by the curability rate in Stage I. Finally this report provides a summary of the diagnostic and prognostic performance measures available from the screening trials to date.

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[in Japanese]

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[in Japanese]

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