[Recent progress on transbronchial lung biopsy].
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Publications and source records attributed to Teruomi Miyazawa.
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OBJECTIVE: To evaluate the efficacy of combined intrapleural therapy with cisplatin, an antineoplastic agent, and OK432, a sclerosing agent, in controlling malignant pleural effusions, when compared with monotherapy with either agent. METHODS: A total of 49 non-small cell lung cancer patients with malignant pleural effusion were randomly assigned to one of three groups: intrapleural cisplatin therapy (n = 17), intrapleural OK432 therapy (n = 17), or both (n = 15). They were compared in terms of success rate, duration of indwelling chest tube and adverse reactions. RESULTS: Rates of pleural effusion recurrence within 180 days following cisplatin, OK432, or combination therapy were 64.7%, 52.9% and 13.3%, respectively, being significantly lower in the combination therapy group (P = 0.01). The mean duration of chest tube drainage was 8.4 days, 5.5 days and 12.9 days, respectively, being significantly longer in the combination therapy group (P < 0.001). All procedures were well tolerated. CONCLUSIONS: Although chest tube drainage took longer because of the time required for multiple administration of the agents, intrapleural combination therapy with cisplatin and OK432 was more effective in controlling malignant pleural effusions due to non-small cell lung cancer than monotherapy with either agent.
Centrally located lung cancers in smokers frequently associated with subsequent primary tumors. We evaluated the telomerase expression chronologically in noncancerous epithelia as a risk factor of susceptibility to lung cancer development. Telomerase protein expression was examined in situ by immunohistochemistry in 26 noncancerous bronchial epithelia adjacent to centrally located early-stage lung cancers in sequential 23 patients treated by photodynamic therapy or surgery among 206 patients who underwent autofluorescence bronchoscopy from 1997 to 2003. Among the 15 lesions in 12 patients treated by photodynamic therapy alone, 11 lesions achieved complete remission after photodynamic therapy, and none of their noncancerous bronchial epithelia was telomerase positive. On the contrary, in the remaining four lesions, either recurrence or secondary lung cancer developed adjacent to the successfully treated primary cancer within 26 months, and the telomerase protein expression in noncancerous epithelia was detected before the secondary cancer development (P < 0.001). The overall relationship of human telomerase reverse transcriptase positivity in noncancerous epithelia and subsequent lung cancer development, including patients treated by radiation or surgery, showed higher significance (P < 0.0001). Histologically "normal" bronchial epithelia in smokers may unphysiologically express telomerase as a field, and such epithelia are likely susceptible to develop lung cancer. We propose that ectopic expression of telomerase in bronchial epithelia may precede transformation in human lung cancer development and that detection of telomerase protein in noncancerous bronchial epithelia will become a useful marker detecting high-risk patients for lung cancer development.
STUDY OBJECTIVES: Endobronchial ultrasonography (EBUS) is used as guidance for transbronchial needle aspiration (TBNA), and real-time imaging of the needle position cannot be confirmed with a single-channel bronchoscope. We assessed the usefulness of EBUS-guided TBNA using a double-channel bronchoscope (EBUS-D), which provides real-time needle position, and compared it with EBUS-guided TBNA using a single-channel bronchoscope (EBUS-S). DESIGN: Randomized, comparative prospective study. SETTING: Hiroshima City Hospital, a tertiary-referral teaching hospital. PATIENTS: Between January 2000 and August 2003, 55 patients with intrathoracic lymphadenopathy were included. Patients were randomized to undergo EBUS-D (n = 30) or EBUS-S (n = 25). METHODS: EBUS-D: The EBUS probe and TBNA catheter were inserted simultaneously through a double-channel bronchoscope. Once the needle placement in the lesion was confirmed by EBUS, TBNA was performed. EBUS-S: The EBUS probe was removed after the determination of the penetration site. Then, the TBNA catheter was inserted and TBNA was performed. RESULTS: All the lymph nodes could be visualized with EBUS in each group of patients. In the EBUS-D group, the TBNA needle was visualized as a hyperechoic point on the real-time EBUS image. The diagnostic accuracy rate of EBUS-D and EBUS-S were statistically significantly different (97% vs 76%, respectively; p = 0.025). On second attempt of TBNA, the diagnostic rate of the EBUS-D group was superior to that of the EBUS-S group (85.7% vs 33.3%, respectively; p = 0.036). The mean number of penetrations was 1.24 in the EBUS-D group and 1.36 in the EBUS-S group. No complications were observed in the EBUS-D group, but a self-limiting hemorrhage occurred in a patient in the EBUS-S group. CONCLUSION: EBUS-D is useful for diagnosing intrathoracic lymphadenopathy, and the obtained specimen with real-time confirmation of the needle is directly proportional to an accurate diagnosis.
Airway stenting at the wave-speed flow-limiting segment (the choke point) is assessed. We determined prospectively the precise location of the choke point using the flow-volume curve, endobronchial ultrasonography, ultrathin bronchoscopy, and three-dimensional computed tomography scan before and after stenting in 64 patients with extrincic compression due to lung cancer. We noted distinct flow-volume curve patterns specific to the type of stenosis. The tracheal stenosis group indicated fixed narrowing patterns with an expiratory plateau, bronchial stenosis group dynamic collapse patterns with an expiratory flow deterioration (choking), carinal stenosis group combined fixed and dynamic patterns, and extensive stenosis group complex patterns containing elements of all the former. After stenting, almost full-function patterns with significant improvement in PEF were observed in all groups (p < 0.01, p < 0.05, p < 0.001, p < 0.01, respectively). In patients with extensive stenosis, implantation of additional stents was required when the choke points were observed to have migrated to the areas of malacia with cartilage destruction by the tumor. Secondary stenting at migrated choke points resulted in a significant improvement in PEF over the initial stenting (p < 0.01). Stenting at the choke point improved expiratory flow limitation by increasing the cross-sectional area, supporting the weakened airway wall and relieving dyspnea.
Endobronchial ultrasonography (EBUS) allows visualization of the tracheobronchial tree with real-time ultrasound and permits visualization of the internal structure of pulmonary lesions, which may narrow the differential diagnosis. The indications for EBUS are to (1) determine the depth of tumor invasion of tracheobronchial lesions, (2) define positional relationships with the pulmonary artery and veins and hilar structures and determine the extent of tumor invasion, (3) visualize paratracheal and peribronchial lymph nodes and metastatic lesions and enable EBUS-guided transbronchial needle aspiration (TBNA), and (4) localize and diagnose peripheral pulmonary lesions (benign or malignant). New and evolving applications of EBUS will increase the cost-effectiveness of EBUS in the diagnosis and treatment of thoracic diseases.
STUDY OBJECTIVE: To assess the ability of endobronchial ultrasonography (EBUS) using a guide sheath (EBUS-GS) to diagnose peripheral pulmonary lesions. METHOD: We devised a technique for EBUS-GS covering a miniature probe, and 150 lesions were evaluated in a prospective open study. In this procedure, the probe covered by a guide sheath is introduced into the lesion via the working channel of a bronchoscope. The probe is withdrawn, while the guide sheath is left in situ. A brush or biopsy forceps is introduced through the guide sheath into the lesion. RESULTS: One hundred sixteen of 150 EBUS-GS procedures (77%) were diagnostic. Cases in which the probe was located within the lesion had a significantly higher diagnostic yield (105 of 121 cases, 87%) than when the probe was located adjacent to it (8 of 19 cases, 42%) [p < 0.0001, chi(2)]. The diagnostic yield from EBUS-GS in lesions </= 10 mm (16 of 21 lesions, 76%), >10 to </= 15 mm (19 of 25 lesions, 76%; p = 0.99, chi(2)), >15 to </= 20 mm (23 of 35 lesions, 66%; p = 0.41, chi(2)), and > 20 to </= 30 mm (33 of 43 lesions, 77%; p = 0.96, chi(2)) were similar, demonstrating the efficacy of EBUS-GS even in lesions </= 10 mm in diameter. In 54 of 81 lesions </= 20 mm, fluoroscopy was not able to confirm whether the forceps reached the lesion. However, the yield was the same with (67%, 18 of 27 lesions) and without (74%, 40 of 54 lesions) successful fluoroscopy (p = 0.96, chi(2)). Moderate bleeding occurred in two patients (1%); there were no other complications. CONCLUSIONS: EBUS-GS is a useful method for collecting samples from peripheral pulmonary lesions, even those too small to be visualized under fluoroscopy.
STUDY OBJECTIVES: To assess the efficacy and complications of interventional bronchoscopic techniques in treating airway stenosis due to tracheobronchial tuberculosis. DESIGN: Case series. SETTING: Respiratory care centers at two tertiary care referral teaching hospitals in Japan, Hiroshima City Hospital and Okayama Red Cross Hospital. PATIENTS AND INTERVENTIONS: A total of 30 patients were admitted to the hospital with a diagnosis of tracheobronchial tuberculosis between January 1991 and January 2002. Of those 11 patients received interventional bronchoscopy, including stent placement, laser photoresection, argon plasma coagulation (APC), balloon dilatation, cryotherapy, and endobronchial ultrasonography (EBUS). One patient with complete bronchial obstruction underwent a left pneumonectomy. RESULTS: Six patients underwent stent placement after balloon dilatation, while the remaining five patients underwent only balloon dilatation. In six patients, Dumon stents were successfully placed to reestablish the patency of the central airways. Two patients first had Ultraflex stents implanted but had problems with granulation tissue formation and stent deterioration caused by metal fatigue due to chronic coughing. Dumon stents then were placed within the Ultraflex stents after the patient had received treatment with APC and mechanical reaming using the bevel of a rigid bronchoscope. In four patients, EBUS images demonstrated the destruction of bronchial cartilage or the thickening of the bronchial wall. The main complications of Dumon stents are migration and granulation tissue formation, necessitating stent removal, or replacement, and the application of cryotherapy to the granuloma at the edge of the stent. CONCLUSION: Interventional bronchoscopy should be considered feasible for management of tuberculous tracheobronchial stenosis. Dumon stents seem to be appropriate, since removal or replacement is always possible. Ultraflex stents should not be used in these circumstances because removal is difficult and their long-term safety is uncertain. EBUS could provide useful information in evaluating the condition of the airway wall in cases of tracheobronchial tuberculosis with potential for bronchoscopic intervention.
Two Japanese women were diagnosed as having well-differentiated adenocarcinoma of the lung with brain metastases. Since it was considered they could not tolerate conventional chemotherapy, we administered gefitinib without any previous systemic therapy. In both patients gefitinib acted dramatically on all the lesions including the brain metastases, resulting in a marked decrease of the elevated CEA levels, and improvement of their quality of life. Retrospective evaluation of epidermal growth factor receptor expression levels by immunohistochemistry revealed positive results in both cases. Though gefitinib has been recommended for patients previously treated with chemotherapy, it should be considered feasible as a first line therapy.
Primary adenocarcinoma of the trachea is rare. We present a case that was successfully treated with radiotherapy followed by surgical resection. A 66-year-old man was admitted to our hospital because of cough, sputum and dyspnea. A chest CT film showed a tracheal tumor, and transtracheal biopsy specimen showed well-differentiated papillary adenocarcinoma. Other examinations excluded the diagnosis of metastatic adenocarcinoma from other organs. Since stenosis of the trachea was rapidly progressive, a tracheal stent was inserted to alleviate the obstruction. After radiotherapy, the tumor size decreased, after which surgical resection was performed. No recurrence had been observed 26 months after the operation.
Photofrin is the most commonly used photosensitizer for photodynamic therapy (PDT). The major side effect of Photofrin is cutaneous photosensitivity. A second generation photosensitizer, mono-L-aspartyl chlorin e6 (NPe6) has shown anti-tumor efficacy and rapid clearance from skin. Therefore, we conducted a phase II clinical study to investigate the anti-tumor effects and safety of NPe6 in patients with early superficial squamous cell carcinoma of the lung. Enrollment criteria consisted of endoscopically evaluated early stage lung cancer with normal chest X-ray and CT images, no lymph node or distant metastasis. Tumors were located no more peripherally than subsegmental bronchi, the peripheral margin had to visible, and the tumor size had to not more than 2 cm in diameter. The histologic type of the tumor had to squamous cell carcinoma. Laser irradiation (100 J/cm2) using a diode laser was performed at 4 h after administration of NPe6 (40 mg/m2). Among 41 patients with 46 lesions, 40 with 45 lesions were eligible for safety evaluation, and 35 patients with 39 lesions were judged as eligible for efficacy evaluation. No serious adverse drug reactions were observed. Disappearance of skin photosensitivity was recognized within 2 weeks in 28 of 33 patients (84.8%) and in all the other seven patients first tested at 15-18 days. Complete response (CR) was seen in 84.6% of lesions (82.9% of patients). This study demonstrated excellent anti-tumor effects and safety, especially low skin photosensitivity in patients with early stage lung cancer. PDT using the second generation photosensitizer NPe6 and a diode laser will likely become a standard modality of PDT for central type early superficial squamous cell carcinoma of the lung.
Relapsing polychondritis (RP) with tracheobronchial involvement has a poor prognosis, and a delay in diagnosis increases morbidity and mortality; however, the diagnosis is difficult to make. Endobronchial ultrasonography (EBUS) revealed changes in the tracheobronchial cartilage in two patients who met the criteria for RP, and facilitated the diagnosis. In these cases, EBUS revealed a poorly defined bronchial wall structure with two patterns of cartilaginous damage: fragmentation and edema. These cases were successfully treated by the implantation of nitinol stents, the sizes of which were determined by EBUS. EBUS was found to be useful in the diagnosis and treatment of RP.
To evaluate the utility of endobronchial ultrasonography (EBUS) in selecting appropriate candidates with centrally located early-stage lung cancer for photodynamic therapy (PDT) with curative intent, we performed EBUS before PDT in 18 biopsy-proven squamous cell carcinomas (including three carcinoma in situ) that had been considered to be appropriate candidates for PDT by conventional bronchoscopy and high-resolution computed tomography (HR-CT). Nine lesions were diagnosed as intracartilaginous by EBUS and subsequently PDT was performed. Long-term complete remission has been achieved in these patients with a median follow-up term after PDT of 32 months. The remaining nine lesions were diagnosed as extracartilaginous by EBUS and were considered candidates for other therapies such as surgical resection, chemotherapy, and radiotherapy, although two were invisible by HR-CT, three were superficial, and five were < or = 1 cm in diameter on observation by bronchoscopy. The depth of tumor invasion estimated by EBUS was proven to be accurate by histopathologic findings in six specimens after surgical resection. We conclude that EBUS is a useful technique that might be considered in addition to conventional bronchoscopy and HR-CT to improve the efficacy of PDT in patients with centrally located early-stage lung cancer.