Aberrant DNA Methylation of NPTX2 as an Indicator of Malignant Behavior in Thymic Epithelial Tumors.

Thymic epithelial tumors (TET) consist of thymomas, thymic carcinoma (TC), and neuroendocrine tumors of the thymus (NECTT). Genetic and epigenetic alterations in TET have been the focus of recent research. In the present study, genome-wide screening was performed on aberrantly methylated CpG islands in TET, and this identified neuronal pentraxin 2 (NTPX2) as a significantly hypermethylated CpG island in TC relative to thymomas. NPTX2 is released from pre-synaptic cells in response to neuronal activity/seizure, and plays a role in host immunity and acute inflammation. TET samples were obtained from 38 thymomas, 25 TC, and 6 NECTT. The DNA methylation, mRNA, and protein expression levels of NPTX2 were examined. The DNA methylation rate of the NPTX2 gene was significantly higher in TC than in the normal thymus and thymomas, except B3. The mRNA expression level of NPTX2 was lower in TC than in the normal thymus. An inverse relationship was observed between mRNA expression levels and methylation levels. Relapse-free survival was shorter in patients with high NPTX2 DNA methylation levels than in those with low DNA methylation levels. NECTT showed very high mRNA and protein expression levels and low DNA methylation levels of NPTX2. NPTX2 may function as a tumor suppressor in TC, and have an oncogenic function in NECTT.

Lung regeneration with rat fetal lung implantation and promotion of alveolar stem cell differentiation by corticosteroids.

Introduction: The lung is a difficult organ to regenerate, and the development of functional lungs has still not been achieved. In this study, we investigated lung regeneration using a rat fetal lung tissue-implanted model. This study aimed to evaluate the functioning of the implanted fetal lung tissue and investigate the graft differentiation and maturation mechanism, focusing on alveolar stem cells. Methods: Fetal lung tissue fragments were obtained from Lewis rats on day 17 and implanted into adult lungs. Animals were divided into the following three groups: group 1, injection into the adult left lung parenchyma; group 2, injection with post-caval lobectomy; and group 3, injection with post-caval lobectomy and corticosteroid administration. Computed tomography was performed on weeks 1, 2, 4, and 8. The presence of alveolar pore, CD31 expression, and bipotential progenitor cell (podoplanin+/surfactant protein C+) localization were histologically evaluated. MiRNA expression was comprehensively compared among the three groups. Results: The grafts comprised type I and type II alveolar cells connected to the recipient lungs with alveolar pores and capillary networks in the interstitial tissue. The alveolar space was the largest and the computed tomography value was the lowest in the grafts of the corticosteroid-administered group. The number of bipotential progenitor cells was the lowest in the corticosteroid administration group on day 7. Moreover, microRNA-487-3p, 374-5p, and 20b-5p expression was changed by more than 2-fold between the post-caval lobectomy and corticosteroid administration groups. Conclusions: Implanted fetal lung tissues established airway and capillary communication with the recipient lungs, and corticosteroids accelerated their maturation by promoting the differentiation of progenitor cells. The study findings provide new insights into lung regeneration research.

[Descending Necrotizing Mediastinitis with Empyema Necessitated Two Performances of Surgical Drainage for Successful Treatment:Report of a Case].

The case was a 57-year-old woman. She visited a local doctor with a chief complaint of sore throat. A retropharyngeal abscess was suspected, and she was referred to our otolaryngology. Contrast-enhanced computed tomography(CT) scan revealed continuous fluid retention from the retropharyngeal space to the neck and the superior and posterior mediastinum with bilateral pleural effusion. The patient was diagnosed with descending necrotizing mediastinitis with empyema, and on the same day cervical drainage, thoracoscopic bilateral mediastinal drainage, empyema curettage and tracheostomy was performed. Postoperative contrast-enhanced CT scan revealed a widespread residual mediastinal abscess and thoracoscopic bilateral mediastinal drainage was performed again on the 11th postoperative day. After reoperation, the inflammation gradually subsided and she was discharged 47 days after reoperation.

[The Postoperative Recurrence of Adenosquamous Cell Carcinoma of the Lung as a Polypoid Mass in the Tracheal Lumen;Report of a Case].

The case is 77 years old, female. She was referred to a local doctor with a chief complaint of cough and wheezing and was treated as asthma. However, symptoms did not improve and she was referred to our hospital. She had a history of right upper lobectomy for lung cancer about 2 years before, with the pathological diagnosis of adenosquamous cell carcinoma, pT1aN0M0, stage I A. Chest computed tomography (CT) scan showed a pedunculated polypoid mass almost occupying the lumen in the trachea immediately above the tracheal bifurcation, and the emergency bronchoscopic resection using a high-frequency snare under general anesthesia was performed. Postoperatively, 50 Gray of radiotherapy was added.

[Endobronchial Hamartoma of the Subsegmental Bronchus;Report of a Case].

The case was 56 years old male. An abnormal shadow was pointed out by chest computed tomography (CT) at a medical examination. The CT scan revealed a 13 mm mass shadow that contacts with the B5a of the right middle lobe. Bronchoscopy revealed a yellow colored lesion that occluded B5ai. A non-cartilage type endobronchial hamartoma was suspected and the biopsy was performed, but a definitive diagnosis was not achieved. The lesion was surgically resected by the right middle lobectomy, and the histopathological diagnosis was an endobronchial hamartoma consisting mainly of mature adipose tissue.

[Synchronous Thymic Carcinoma and Primary Lung Cancer].

A 79-year-old woman visited a local doctor with a chief complaint of cough. A computed tomography (CT) scan revealed an anterior mediastinal tumor and 20 mm sized ground-glass nodule (GGN) in the right upper lobe. Bronchoscopy was performed, but no definitive diagnosis was made for GGN and follow-up observation was made with an image. The anterior mediastinal tumor was a solid tumor of 50 mm in size, and invasive thymoma was suspected. A total thymectomy with pericardial partial resection was performed through a median sternotomy. Histopathological diagnosis was squamous cell carcinoma, and no pericardial infiltration was observed. On the other hand, GGN of the right upper lobe during follow-up increased in size and thoracoscopic surgery was performed 3 months after surgery for thymic carcinoma. Adenocarcinoma was diagnosed by rapid diagnosis and the upper lobectomy with lymph node dissection were conducted. No signs of recurrence have been observed for 5 years after operation.

[Bronchogenic Cyst in the Anterior Mediastinum;Report of a Case].

The case is 61 years old, female. The mediastinal mass was pointed out at a medical examination, and she visited our hospital. A plain computed tomography (CT) scan showed a 12×35 mm mass in the anterior mediastinum, and a thymoma was suspected. Magnetic resonance imaging( MRI) showed low signal at T1-weighted image and high signal at T2-weighted image. A benign cystic mass such as a thymic cyst and a pericardial cyst was suspected, and thoracoscopic resection was performed. Pathologically, a bronchogenic cyst was diagnosed.

[Primary Pleomorphic Rhabdomyosarcoma of the Chest Wall;Report of a Case].

The case was 70 years old, female. She visited a nearby hospital complaining of a mass in the right breast which was diagnosed as a chest wall tumor and referred to our department. A computed tomography (CT) scan revealed a 10 cm-sized contrast enhanced mass with bone destruction of the 3rd and 4th ribs. Invasion to the mammary gland tissue was not observed. A malignant tumor was suspected by percutaneous needle biopsy and the tumor was excised with the chest wall including the 3rd, 4th and 5th ribs. Histopathological diagnosis was a pleomorphic rhabdomyosarcoma. No signs of recurrence have been observed for 5 years after the operation.

[Utility of Prophylactic Administration of Pegfilgrastim in Breast Cancer Chemotherapy].

Febrile neutropenia(FN)is a frequent adverse event observed in cancer patients undergoing chemotherapy that may cause life-threatening infections. However, reducing the dose of anti-cancer drugs for breast cancer in adjuvant settings to prevent FN has been reported to adversely affect patient survival. Therefore, it is important to administer therapeutic agents as per their prescheduled regimens without delays or reductions in the dosage. From April 2015 to September 2017, pegfilgrastim was administered to 24 patients with breast cancer(primary prevention in 11 patients and secondary prevention in 13 patients)to prevent FN during chemotherapy in either adjuvant or metastatic settings. We were able to reduce the incidence of FN through prophylactic administration of pegfilgrastim without encountering serious adverse events. The inclusion of pegfilgrastim is considered essential for the safe administration of chemotherapy according to a preplanned schedule. Here, we discuss the indications, efficacy, and safety of the drug.

Candidate biomarkers predictive of anthracycline and taxane efficacy against breast cancer.

BACKGROUND: Since breast cancer shows diversity in clinical behaviors, a standard therapy does not always lead to favorable outcomes. MATERIALS AND METHODS: The expression statuses of candidate markers, including topoisomerase-II alpha (TOP2A), beta-tubulin (B-tub), and tissue inhibitor of metalloprotease-1 (TIMP-1), were immunohistochemically evaluated in 70 breast cancer tissues from 68 patients with advanced breast cancers receiving chemotherapy. RESULTS: The response rates to anthracycline and taxane were 70.5% and 67.2%, respectively. Overall, 25.1% ± 29.7%, 8.32% ± 10.1%, and 16.37% ±17.5% of cancer cells in the tumors studied were positive for B-tub, TOP2A, and TIMP-1 expressions, respectively. However, positive molecule expression did not differ between patients who did and did not exhibit clinical responses to treatment. The proportion of TOP2A-positive cancer cells was significantly higher among anthracycline responders than among nonresponders in HR-negative cancer (15.4% ±17.5% vs. 2.0% ± 2.4%, respectively, P = 0.048), whereas TOP2A and TIMP-1 expression statuses did not differ in HR-positive cancer. When patients were stratified according to B-tub, TOP2A, or TIMP-1 expression statuses (B-tub ≥10% vs. <10%, TOP2A ≥5% vs. <5%, TIMP-1 ≤20% vs. >20%, respectively), the proportion of patients with ≥10% B-tub-positive cancer cells was significantly higher in taxane responders than in nonresponders (72.4% vs. 37.5%, respectively, P = 0.016). Anthracycline responders showed a trend to have a higher proportion of patients with either ≥5% TOP2A-positive cancer cells or ≤20% TIMP-1-positive cancer cells compared to nonresponders (86.7% vs. 61.5%, respectively, P = 0.066). CONCLUSION: Immunohistochemical TOP2A, TIMP-1, and B-tub expression analyses are expected to be useful for predicting tumor responses to chemotherapy.

Lung regeneration by fetal lung tissue implantation in a mouse pulmonary emphysema model.

The mortality and morbidity of chronic obstructive pulmonary disease are high. However, no radical therapy has been developed to date. The purpose of this study was to evaluate whether fetal mouse lung tissue can grow and differentiate in the emphysematous lung. Fetal lung tissue from green fluorescent protein C57BL/6 mice at 16 days' gestation was used as donor material. Twelve-month-old pallid mice were used as recipients. Donor lungs were cut into small pieces and implanted into the recipient left lung by performing thoracotomy under anesthesia. The recipient mice were sacrificed at day 7, 14, and 28 after implantation and used for histological examination. Well-developed spontaneous pulmonary emphysema was seen in 12-month-old pallid mice. Smooth and continuous connection between implanted fetal lung tissue and recipient lung was recognized. Air space expansion and donor tissue differentiation were observed over time. We could clearly distinguish the border zones between injected tissue and native tissue by the green fluorescence of grafts. Fetal mouse lung fragments survived and differentiated in the emphysematous lung of pallid mice. Implantation of fetal lung tissue in pallid mice might lead to further lung regeneration research from the perspective of respiratory and exercise function. J. Med. Invest. 63: 182-186, August, 2016.

Holter ECG monitoring of sympathovagal fluctuation during bronchoscopy.

BACKGROUND AND AIMS: The changes of autonomic nervous activity during bronchoscopic procedures are closely related to the development of cardiovascular complications. We aimed to evaluate the changes of autonomic nervous activity during bronchoscopic procedures using R-R interval variability from electrocardiograms (ECGs) obtained during diagnostic bronchoscopy. METHODS: Twenty-four patients who underwent bronchoscopy were included. Continuous ECG was recorded prior to, during and after the bronchoscopic procedure. Time and frequency domain analyses of heart rate variability were performed. RESULTS: Heart rate increased significantly after pre-medication compared with that before pre-medication and increased further during bronchoscopy. The coefficient of variation (CVRR ) values after pre-medication and during bronchoscopy were significantly higher than those before pre-medication (P = 0.031 and P = 0.041, respectively). The low frequency (LF) power decreased during bronchoscopy. LF powers obtained after bronchoscopy were significantly lower than those obtained before bronchoscopy (P < 0.041). The high-frequency (HF) power was found to be decreased during bronchoscopy. In particular, HF powers obtained after bronchoscopy were significantly lower than those obtained before bronchoscopy (P < 0.019). Although the LF/HF ratios increased after pre-medication, they decreased temporarily during the bronchoscope insertion. CONCLUSIONS: This study shows for the first time that Holter ECG monitoring during diagnostic bronchoscopy was associated with activation of cardiac sympathetic and withdrawal of cardiac parasympathetic regulation, which may contribute to the occurrence of cardiac events during bronchoscopic procedures. So, Holter ECG monitoring during bronchoscopic procedures may confer reduction in cardiovascular events.

Comprehensive evaluation of the response of genes to the administration of the antitumor drug S-1 using a low density array.

S-1 is a newly developed dihydropyrimidine dehydrogenase inhibitory fluoropyrimidine that exhibits high clinical efficacy against non-small cell lung cancers. To identify genes that may be associated with chemosensitivity to the antitumor drug S-1, we used a low density array representing 93 genes to analyze expression profiles in 4 orthotopically implanted lung cancers derived from human lung cancer cell lines (Lu99, Lu130, LC6 and A549). The tumor growth inhibition (TGI) rates of S-1 in orthotopically implanted tumors of the Lu99, Lu130, LC6 and A549 cell lines were 34.6, 37.5, 32.1 and 3.6%, respectively. The expression of the PRSS3, ABCC4, TXN, SHMT1 and CMPK genes was significantly promoted in the orthotopically implanted SCID mouse model of the 4 lung cancer cell lines by the administration of S-1, while the expression of the LMO7 and FOLH1 genes was significantly suppressed. The expression of the ABCC1, 2 and TST genes was negatively correlated with TGI. The expression of the TK1 and ERCC2 genes was positively correlated with TGI. The results of the present study suggest that the expression of the ABCC1, 2, TST, TK1 and ERCC2 genes is related to resistance to the antitumor drug S-1.

Monitoring of exhaled carbon monoxide and carbon dioxide during lung cancer operation.

OBJECTIVE: Carbon monoxide (CO) is expelled mainly via the lungs, so that exhaled carbon monoxide (Ex-CO) concentration reflects endogenous production. Recent reports have shown that Ex-CO levels are increased in critically ill patients and after anaesthesia and surgery. However, there has been no investigation of the changes in Ex-CO level during a lung operation. We continuously monitored Ex-CO and exhaled carbon dioxide (Ex-CO2) concentrations during surgery for lung cancer. METHODS: Eighteen lung cancer patients who underwent elective lung cancer lobectomy were enrolled in this study. All patients were endotracheally intubated and ventilated under general anaesthesia. Ex-CO and Ex-CO2 concentrations were separately monitored and recorded continuously using two sets of Carbolyzer® breath analysers (Taiyo Inc., Osaka, Japan). RESULTS: Ex-CO concentration increased rapidly in response to changes in body position from supine to decubitus and was significantly decreased when patients were once again lying back (supine 2). Upon restarting bilateral ventilation, Ex-CO concentration in the operated lung was significantly higher than that in the breathing lung. In the lateral decubitus position, Ex-CO2 concentration showed the same pattern of increase as seen for Ex-CO. In the operated lung, the Ex-CO2 concentrations changed significantly at clamping, declamping and supine 2. In the re-ventilated, operated lung, the Ex-CO2 concentration was significantly lower than in the breathing lung. In the breathing lung, the Ex-CO2 concentration did not exhibit any significant changes over the course of the operation. CONCLUSIONS: When breathing was restarted, the Ex-CO level of the target lung was significantly higher than that of the breathing lung. The Ex-CO concentration was also affected by the surgical body position and this change was marked and transient.

18F-fluorodeoxyglucose positron emission tomography/computed tomography and the relationship between fluorodeoxyglucose uptake and the expression of hypoxia-inducible factor-1α, glucose transporter-1 and vascular endothelial growth factor in thymic epithelial tumours.

OBJECTIVES: The objective of this study was to evaluate the usefulness of (18)F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) and the relationships among the expressions of hypoxia-inducible factor-1α (HIF-1α), glucose transporter-1 (Glut-1) and vascular endothelial growth factor (VEGF), histological type, other clinical factors and FDG uptake in thymic epithelial tumours. METHODS: Thirty-three patients who underwent FDG-PET/CT before treatment were reviewed. All types of tumours were reclassified into three subgroups: low-risk thymomas (types A, AB and B1), high-risk thymomas (types B2 and B3) and thymic carcinomas. Tumour contour, pattern of FDG uptake, tumour size and maximum standardized uptake value (SUVmax) were obtained. Expressions of HIF-1α, Glut-1 and VEGF were analysed immunohistochemically, and these expressions were evaluated using grading scales. RESULTS: FDG uptake was visually recognized in all (100%) tumours. A homogeneous pattern of FDG uptake was increasingly observed in the order of low-risk thymomas to high-risk thymomas to thymic carcinomas (P = 0.016). SUVmax for thymic carcinomas was significantly higher than that for thymomas (P = 0.008). With the optimal cut-off value of SUVmax of 5.6, the sensitivity, specificity and accuracy for diagnosing thymic carcinoma were 0.75, 0.80 and 0.79, respectively. Regarding the mean scoring of HIF-1α, Glut-1 and VEGF, increasing trends were observed in the order of low-risk thymomas to high-risk thymomas to thymic carcinomas. Tumour size revealed a significant correlation with SUVmax (r = 0.60, P < 0.001), and the expression of HIF-1α showed a moderate association, but the expression of Glut-1 showed no correlation with SUVmax. Regarding correlations between the expression of the three markers, there were moderate associations between HIF-1α and Glut-1, and HIF-1α and VEGF, and a significant correlation between Glut-1 and VEGF (r = 0.60, P < 0.001). In type B1 thymoma, HIF-1α and Glut-1 were partly expressed in non-neoplastic immature lymphocytes. CONCLUSIONS: FDG-PET/CT should be performed in patients with tumours in the anterior mediastinum because the pattern of FDG uptake and SUVmax are useful in the differential diagnosis of thymic epithelial tumours. Furthermore, the expressions of HIF-1α, Glut-1 and VEGF might be associated with malignancy of thymic epithelial tumours. In contrast, FDG uptake might be dependent on tumour size rather than Glut-1 overexpression.

Fluoroscopy-assisted thoracoscopic resection after computed tomography-guided bronchoscopic metallic coil marking for small peripheral pulmonary lesions.

OBJECTIVES: To re-evaluate the efficacy of fluoroscopy-assisted thoracoscopic resection after computed tomography (CT)-guided bronchoscopic metallic coil marking (FATS-CM), which was our original method for small peripheral pulmonary lesions. METHODS: Fifty-eight patients with 63 lesions underwent FATS-CM. A metallic coil was installed in the bronchus nearest to the lesion under CT fluoroscopic guidance with ultrathin bronchoscopy. The virtual bronchoscopic navigation (VBN) system was used in 14 cases. Afterwards, we basically performed wide wedge resection (WWR) using a C-arm-shaped roentgenographic fluoroscope during thoracoscopic surgery initially, and then the final procedure was determined by intraoperative histological diagnosis. Moreover, we prospectively treated ground-glass opacity (GGO) lesions of <20 mm diameter according to our treatment protocol from September 2004. RESULTS: We could install coils in the objective bronchi in all cases. The average time required for the marking procedure was 38.9 (15-120) min. Pneumothorax was recognized in 1 (1.7%) case as a complication, but no fatal complications occurred. We could also install coils for each lesion in 4 cases (9 lesions) with multiple lesions. In 14 cases with the VBN system, the examination time and CT number were significantly reduced (P < 0.05 and <0.001, respectively), compared with those of 40 cases without the VBN system. The average interval between the CM and the operation was 5.6 (0-30) days. We never experienced a case of migration preoperatively. Sixty-two (98.4%) lesions were definitively identified, and WWRs were performed using three trocars in 58 (92.1%) cases during thoracoscopic surgery. Lobectomy was initially performed in only 1 case owing to coil migration. Thirty-seven of 40 cases (92.5%) were in line with the treatment protocol. There were no local-regional recurrences in all cases undergoing WWR. CONCLUSIONS: We could prospectively show that our method was suitable to perform WWR with a sufficient margin for small GGO lesions of <20 mm. Moreover, we reconfirmed that the advantages of our method were safety, permitting flexibility in scheduling operations and a high ability to deal with multiple lesions. Additionally, our method became a minimally invasive and mature technique by using a new VBN system.

18F-fluorodeoxyglucose positron emission tomography/computed tomography is useful in postoperative follow-up of asymptomatic non-small-cell lung cancer patients.

OBJECTIVES: Postoperative follow-up and surveillance after curative resection for non-small-cell lung cancer (NSCLC) patients are generally performed. However, there is no consensus on the best programme at this time. The aim of this study was to evaluate the diagnostic capability of (18)F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) in postoperative NSCLC patients without clinical and radiological evidence of recurrence, as a follow-up and surveillance programme. METHODS: Between January 2005 and April 2010, a total of 101 NSCLC patients underwent potentially curative operations and follow-up FDG-PET/CT was performed in patients without clinical and radiological evidence of recurrence at least once a year in principle. A total of 233 FDG-PET/CT studies were entered and retrospectively reviewed. RESULTS: Eighteen (18%) asymptomatic patients had recurrent diseases and 22 recurrent sites were confirmed. Of 22 recurrent sites, recurrence was diagnosed by histological examination in 9 (41%) sites and by imaging examination in 13 (59%) sites. FDG-PET/CT correctly diagnosed recurrence in 17 of the 18 (94%) patients and 21 of the 22 (95%) recurrent sites. The sensitivity, specificity, positive predictive value, negative predictive value and accuracy were 94.4, 97.6, 89.5, 98.8 and 97.0%, respectively. On the other hand, in 3 patients, other diseases were detected and treated appropriately. Post-recurrence therapies were performed in all patients with recurrence, but 4 (22%) patients died of the original diseases. The median post-recurrence survival was 25.2 months, and the 1- and 2-year post-recurrence survival rates were 83.3 and 69.6%, respectively. CONCLUSIONS: FDG-PET/CT is a useful tool that has high capability to detect recurrences in asymptomatic NSCLC patients after a potentially curative operation. However, a large-scale multi-institutional randomized control trial may be needed to ascertain the benefit of surveillance with FDG-PET/CT.

Implantation of fetal rat lung fragments into bleomycin-induced pulmonary fibrosis.

OBJECTIVE: Pulmonary fibrosis is a life-threatening disease that results in progressive respiratory failure. We have suggested the possibility of fetal lung tissue as an option for further investigation into lung regeneration. The objective was to prove whether fetal lung fragments can survive and differentiate in fibrotic lung. METHODS: Lewis rats were administered bleomycin and used as recipients after 3 or 4 weeks. Day 17 fetal lung tissue from green fluorescent protein Lewis rats was used as donor material. Donor lungs were removed, cut into small pieces, and implanted into the recipients' left lung. The recipients received cyclosporin to prevent immune response to green fluorescent protein and were killed after 1, 2, 4, 8, and 12 weeks and histologically evaluated. Furthermore, the expression of thyroid transcription factor-1 and Clara cell secretory protein in the implanted fetal lung tissue was immunohistologically evaluated. RESULTS: Fibrotic changes were recognized for a long period of time in the recipient lungs. The implanted fetal lung fragments could be clearly distinguished from recipient lungs because of the luminescence of grafts. Fetal lung fragments could survive in the recipient lungs with fibrotic changes. The air spaces of implanted fetal lungs were narrow at 1 and 2 weeks but expanded with the passage of time. The connection between the recipient lung and the implanted fetal lung was recognized, particularly in the peripheral grafts. The expression patterns of thyroid transcription factor-1 and Clara cell secretory protein in implanted lungs resembled those in the process of normal lung morphogenesis. CONCLUSIONS: Fetal rat lung fragments could survive and differentiate in bleomycin-induced completely fibrotic lung.

Follow-up using fluorescence bronchoscopy for the patients with photodynamic therapy treated early lung cancer.

PURPOSE: To evaluate the accuracy of fluorescence bronchoscopy by precise histological analysis of the photodynamic therapy (PDT) treated lesions. METHODS: A retrospective study was conducted on thirteen patients (16 lesions) with centrally located early lung cancer (CLELC) had been undergone photodynamic therapy and had been followed up by fluorescence bronchoscopy. Fluorescence bronchoscopy was performed between 1 and 60 months after photodynamic therapy. RESULTS: Of the 16 early carcinomas treated, 14 (87.5%) had a CR, 2 (12.5%) had a NR after initial PDT. Among the 14 carcinomas achieving a CR, 4 (29%) recurred locally from 6 to 12 months after initial PDT. A total of 62 surveillance auto fluorescence bronchoscopies (average; 4.5/patient) and 47 biopsies (average; 4/patient) were performed after PDT. The addition of the SAFE-3000 examination to conventional bronchoscopy increased the sensitivity of screening from 69% to 100%, which yielded a relative sensitivity of 145% with a negative predictive value of 100%. Out of 14 CR lesions, 9 lesions finally reverted to normal fluorescence. CR cases that did not show normal fluorescence were relapsed cases or a patient with complete response whose treated lesion showed fibrosis in the sub mucosa. Histopathological finding of the complete response sites which demonstrated temporal fluorescent defect consisted of inflammatory lesions, goblet cell hyperplasia, basal cell hyperplasia, squamous metaplasia or dysplasia. CONCLUSION: our results confirm that SAFE-3000 allows accurate assessment of the quality and efficacy of PDT.