Background. Although sputum cytology is the only way to detect early hilar lung cancer in lung cancer screening, there are also various problems. Therefore, the subcommittees concerning sputum cytology was established in each the Japan Lung Cancer Society and the Japanese Society of Clinical Cytology, and in a joint effort with the Japan Society for Respiratory Endoscopy, the investigation of these problems were reported by the committee of the three societies. We concluded that confirming the usefulness of sputum cytology at present is the inevitable and the most important issue. Objective. We clarified the actual situation of diagnosis for early hilar lung cancer in Japan by a questionnaire. Subject and Methods. We sent questionnaires to authorized and associated institutes of the Japan Society for Respiratory Endoscopy, and respondents were questioned concerning the following items. The basic items were a) the number of bronchoscopies performed, b) the number of lung cancer resections, c) the number of diagnoses of new early hilar lung cancer, d) the modes of detection, e) histological type, f) treatment modalities that can be estimated in each institute from 2006 to 2007. Moreover, to the extent possible, we ask them to respond to g) the number of advanced hilar squamous cell carcinomas, h) the number of sputum cytology examinations that were found to be positive or suspected to be positive, i) the number of peripheral lung cancers detected by sputum cytology, j) the number of cancers in otorhinological field or esophageal cancers detected by sputum cytology. Results and the Estimated Number of Diagnosis in Japan. The questionnaires were sent to 504 authorized and associated institutes of the Japan Society for Respiratory Endoscopy and returned from 308 (61.1%) of them. These institutes, in the cases of primary lung cancer resections, covered 57.1% of the field study result of the Japanese Association of General Thoracic Surgery. A total of 150 diagnosed cases of early hilar lung cancer in a year were reported. By the reported number and the covering ratio, the number of early hilar lung cancer diagnosis was estimated between 154 and 270 cases per year. Also, 4,000 cases of hilar squamous cell carcinoma in a year in Japan were estimated. Concerning the mode of detection, sputum cytology was the most numerous, accounting for 90% of squamous cell carcinomas; however, the rate of early cancer was less than 10% of hilar squamous cell carcinoma, and moreover, there were regional differences in the detection rates. Conclusions. The national survey of hilar lung cancer suggested that there were 4,000 patients with hilar squamous cell carcinoma at present. However, the ratio of early cancer was less than 10%, and the regional differences in the ratio of early to not early hilar squamous cell carcinoma were also suggested. Based on these, there might have been more opportunities of early diagnosis of hilar lung cancer than were actually diagnosed. Further quality control and much more sputum cytologic examinations for lung cancer screening is recommended.

View full abstract

Objective. The aim of the present study was to define the usefulness of a urine tumor marker, diacetylspermine (DiAcSpm) in patients with lung cancer. Materials and Methods. Of the patients who were treated for lung cancer from August 2003 to September 2010 in our hospital, 308 (non-small cell lung cancer-296, small cell lung cancer-12) were enrolled in this study. We compared the urine tumor marker, DiAcSpm with serum tumor markers (CEA, CYFRA21-1 and Pro-GRP). Results. The sensitivity of urine DiAcSpm (46.4%) was significantly higher than that of serum CEA (32.7%) and serum CYFRA21-1 (23.7%). The specificity of urine DiAcSpm (90.6%) was similar to that of serum CEA (87.5%) and serum CYFRA21-1 (93.8%). We then compared the sensitivities of DiAcSpm and other markers among subjects according to tumor stage. The sensitivity of DiAcSpm was higher than that of CYFRA21-1 in Stage IA and IB patients, and CEA in Stage IIIB and IV patients, while the proportion of positive results for each marker increased with progression of the cancer. In particular, DiAcSpm was markedly elevated in 25.5% and 42.6% of Stage IA and IB patients, respectively, whereas only 5.4% and 18.5% of these patients were CYFRA21-1-positive, respectively. Pathologically, the sensitivity of urine DiAcSpm was markedly higher in patients with adenocarcinoma (39.5%) compared to CYFRA21-1 (17.3%), and in squamous cell carcinoma (62.0%) compared with CEA (33.3%) and SCC antigen (49.0%). Conclusion. These results suggest that urine DiAcSpm is useful as a tumor marker for lung cancer, because it is more sensitive than the serum markers currently in clinical use.

View full abstract

Background. In primary lung cancer cases without visceral pleura invasion or dissemination, cancer cells are rarely confirmed in the pleural effusion intraoperatively. The clinicopathologic findings are thus important for TNM staging by providing the natural history of the disease progression, although the precise mechanisms remain unclear. Case. A 68-year-old man with bloody sputum was given a diagnosis of lung adenocarcinoma arising from the left upper lobe. The clinical TNM stage was IA (cT1bN0M0). He underwent left upper lobe lobectomy and lymph node dissection (ND2a) with video-assisted thoracoscopic surgery. The intraoperative findings revealed minor serous pleural effusion, but there was no pleural invasion or pleural dissemination. His surgical diagnosis was sT1bN0M0D0E1 (+) serousPL0PM0: stage IA, and the histopathologic diagnosis was mixed adenocarcinoma with hilar lymph node metastasis (N1). No extra-nodal invasion was observed. Microscopic examination did not show any invasion of the visceral pleura (PL0), but cancer cells were noted in the pleural effusion on cytological examination. The final histopathologic TNM stage was determined as pT1bN1 (#11) M1a (E+), stage IV. Conclusion. We report a rare case of primary lung cancer with malignant pleural effusion but without visceral pleural invasion. Malignant pleural effusion is an important factor for TNM staging and for determining the treatment strategies for lung cancer. During surgery, even if no visceral pleura invasion is noted, intraoperative lavage or pleural effusion cytology should be routinely performed.

View full abstract

Background. There are few reports of small-cell lung carcinoma (SCLC) with epidermal growth factor receptor (EGFR) gene mutation and the optimal treatment with EGFR-tyrosine kinase inhibitor (EGFR-TKI) for such patients has not yet been established. Case. A 74-year-old woman with dyspnea was referred to our hospital. A chest X-ray showed left pleural effusion and the mediastinum had shifted to the right. A chest CT image after drainage of her pleural effusion revealed a mass in the left lower lobe with destruction of the spine and ribs, and multiple other lesions (cT4N2M1b). The cytological diagnosis of SCLC was confirmed from pleural effusion specimens. Since SCLC is uncommon in non-smoking patients, we performed screening for EGFR mutations which revealed the presence of an exon 18 replacement mutation (G719C). Although first-line chemotherapy with carboplatin and etoposide was initially effective, her general condition worsened due to disease progression. Gefitinib was tried as a second-line therapy, but it was ineffective. Subsequent chemotherapy with amrubicin was also ineffective and the patient died. Conclusion. We encountered a case of SCLC with EGFR gene mutation in a non-smoker. The efficacy of EGFR-TKI for EGFR-mutated SCLC should be investigated further.

View full abstract

Background. Solitary bronchial papilloma is a relatively rare benign tumor, and mixed squamous cell and glandular papilloma is an extremely rare subtype with only 13 cases, including the present case in the literature. Surgical resection is the usual treatment of choice for solitary bronchial papilloma. Case. An 84-year-old woman presented with an abnormal shadow in the right middle lung field detected on a chest X-ray film on an annual check up. A chest CT scan showed partial atelectasis of the right S³ and a protruding tumor shadow in the right main bronchus. A bronchoscopic examination revealed a polypoid tumor in the truncus intermedius, and a biopsy specimen yielded a histological diagnosis of mixed papilloma. The patient underwent endoscopy using an electrosurgical snare and diode laser, because malignant change in the papilloma could not be excluded. The histopathological diagnosis of the resected tumor was a solitary bronchial papilloma of mixed squamous cell and glandular type but without any malignant component. Immunohistochemically, the squamous epithelium was negative for the human papilloma virus (types 6, 11, 18). No recurrence of the tumor has been detected 2.5 years after endoscopic resection. Conclusion. We report a case of solitary bronchial papilloma of mixed squamous cell and glandular type resected by endoscopy. Endoscopy using an electrosurgical snare and diode laser is useful treatment for solitary bronchial papilloma.

View full abstract

Background. Pulmonary actinomycosis is a chronic granulomatous disease caused by Actinomyces israelii, an anaerobic bacterium which is commonly found in the mouth or alimentary tract. It is often difficult to differentiate pulmonary actinomycosis from lung cancer on diagnostic imaging. Case. A 61-year-old woman visited our hospital with a chief complaint of bloody sputum. Chest computed tomography showed a neoplastic lesion with cavities and pleural indentations in the right posterior segment (S²). Bronchial washing and exfoliative cytological findings of bronchoscopic lavage fluid and cells showed class II, respectively. A diagnosis of lung cancer could not be excluded as the patient's serum CEA level was 11.7 ng/ml and she showed a standardizad uptake value (SUV) max of 6.11 on positron-emission tomography. We performed video-assisted thoracoscopic surgery (VATS) of the right upper lobe for diagnosis and treatment and pathologic examination revealed pulmonary actinomycosis. Conclusion. We consider that it may be necessary to perform an invasive surgical procedure such as VATS for curative treatment of pulmonary actinomycosis.

View full abstract

Background. Pulmonary spindle-cell carcinoma is a rare type of poorly differentiated non-small cell lung cancer which consists only of spindle cells, and gastric metastasis from lung cancer is uncommon. Case. A 65-year-old man was admitted to our hospital because of coughing and bloody sputum. Chest computed tomography revealed a large mass extending from the right lower lobe to the mediastinum. We diagnosed non-small cell lung cancer (T4N2M0: stage IIIB) based on transbronchial exfoliative cytology findings. We administered 3 courses of systemic chemotherapy consisting of cisplatin and vinorelbine. However, the tumor increased in size, which resulted in the patient experiencing difficulty in swallowing due to stricture of the esophagus. Therefore, we inserted an esophageal stent in the lower thoracic esophagus. Gastroendoscopy revealed a submucosal tumor and an ulcerative lesion in the body of the stomach. Five months after admission, the patient died of respiratory failure due to multiple lung abscesses. A pathologic examination on autopsy revealed that the tumor cells in the lung and stomach consisted only of spindle cells. Immunohistochemical staining for cytokeratin 7 and vimentin was positive in the tumor cells. Conclusion. We report herein a rare case of pulmonary spindle-cell carcinoma with metastases to the stomach. Pulmonary spindle-cell carcinoma and gastric metastasis from lung cancer are considered to have poor prognoses. Further investigation is needed to understand this disease and to establish the optimal treatment.

View full abstract

Background. Combined small cell lung carcinoma (CSCLC) is histologically classified as the only variant of small cell carcinoma (SCLC). We report a case of CSCLC, that was finally diagnosed by surgery after a long series of chemotherapy treatments for local recurrence of SCLC. Case. A 67-year-old man presented with a tumor 20 mm in diameter, located in the left S⁶. Transbronchial lung curetting cytology revealed SCLC. Stage IIIA (cT1N2M0) SCLC was diagnosed by systemic examination. Concurrent chemo-radiotherapy (cisplatin+etoposide, 40 Gy/20 Fr) was administered and 4 cycles of sequential chemotherapy (carboplatin+etoposide) was performed. The lesion then disappeared completely. Local recurrence at the primary site subsequently occurred twice in 3 years, and was treated with carboplatin+etoposide every time. Tumor was disappeared by chemotherapy at the first recurrence. However, at the second recurrence, the effect to chemotherapy was partial response (PR) and tumor increased only 2 months later. There was no evidence of metastasis to lymph nodes and other tissues by examination including positron emission tomography with ¹⁸F-fluorodeoxyglucose (FDG-PET). Since recurrence occurred at the primary site every time, left lower lobectomy was performed. Histopathological examination showed SCLC with an element of adenocarcinoma. We finally diagnosed CSCLC and added 4 cycles of adjuvant chemotherapy with amrubicin. No relapse has since been seen, as of 5 years after surgery. Conclusion. SCLC has the possibility of containing a non-small cell carcinoma component. In cases with repeated local recurrence, surgical resection is one potential method of therapy.

View full abstract

Background. Whole-brain radiation therapy (WBRT) is widely applied in cases of brain metastases of non-small cell lung cancer (NSCLC) . However, there are few case reports on hemorrhages of brain metastases occurring after WBRT. Case. A 63-year-old woman was given a diagnosis of stage IV (T4N0M1b) lung adenocarcinoma about 4 years previously, and received chemotherapy regimens and gamma knife radiosurgery. However, her brain metastases exacerbated and she received WBRT in November 2010 and docetaxel monotherapy in December 2010. Two weeks after completing WBRT, she experienced dysarthria and an MRI showed multiple hemorrhages within brain metastases. Over a period of careful observation, these hemorrhages repeatedly alternated between improvement and exacerbation. Conclusion. Radiotherapy for metastatic brain tumors is considered to suppress hemorrhagic events of brain metastases. However, multiple intracranial hemorrhages of brain metastases occurred after WBRT in the present case. The accumulation of further studies of similar cases is necessary to identify the exact mechanism of these hemorrhages.

View full abstract

Background. Pulmonary epithelioid hemangioendothelioma (PEH) is a vascular tumor characterized by the growth of vascular endothelial cells. Because of its characteristic of low-to-intermediate grade malignancy, PEH usually grows very slowly and needs differential diagnoses from the various metastatic malignant tumors. The imaging findings are usually non-specific, and in many cases, preoperative diagnosis by bronchoscopy is difficult. We report a case of PEH diagnosed by thoracoscopic lung biopsy. Case. A 33-year-old woman underwent chest radiography screening, which showed multiple nodular shadows in both lungs. A chest computed tomography (CT) scan revealed multiple nodules in both lungs. We suspected tumor metastases, and performed systemic screening for possible primary tumors, but the results were negative. Therefore, we performed video-assisted thoracoscopic lung biopsy, and a pathological diagnosis of PEH was made. Conclusion. The preoperative diagnosis of PEH by imaging or bronchoscopy is usually difficult, and lung biopsy is essential. Moreover, the prognosis remains uncertain even in the absence of prognostic factors. There is no established treatment method for PEH and therefore, long-term follow-up needs to be conducted.

View full abstract

Background. Recently, the establishment of a palliative care team (PCT) in general hospitals in Japan has become common for the enhancement of supportive care of patients with advanced-stage cancer. We encountered a case in which total pain management by a PCT intervention obtained adequate relief from intractable physical pain in a lung cancer patient. Case. A 56-year-old woman with intractable pain in her right chest wall was admitted to our hospital. She had undergone chemotherapy for 2 years previously for advanced non-small cell lung cancer. After the completion of chemotherapy, she gradually developed continuous pain in her chest and was referred to the PCT of our hospital. The cause of her pain was considered to be direct tumor invasion to her chest wall. Treatment of increasing dose of fentanyl was subsequently initiated along with appropriate rescue dose. However, this regimen failed to adequately relieve her pain. At that time, she wanted to make a written will. Since we considered that it might be an effective method for relieving her mental distress, we helped her to prepare it. Her physical pain rapidly disappeared after the preparation of her will, and it remained resolved for about 10 days until she died. Conclusion. The present case suggests that the patient's mental distress and physical pain were closely related, and that total pain management by a PCT intervention helped her gain adequate relief from previously intractable physical pain.

View full abstract