Kazuyuki Oda

Treatment strategy for patients with small peripheral lung lesion(s): intermediate-term results of prospective study

BACKGROUND This prospective study was undertaken to establish a novel management algorithm using new indicators to decide the type of lung resection for small peripheral lung lesions. METHODS Inclusion criteria were: (1) <or=20mm peripheral lung lesion(s) and (2) absence of significant lymph node swelling on preoperative CT. Along with the conventional criteria, the percentage of ground-glass opacity (GGO) (>or=50% as GGO type and <50% as solid type) on high-resolution CT scan was employed. In accordance with such indicators, a wide wedge resection (WWR), segmentectomy or lobectomy was planned for individual patients. The primary endpoint was to estimate the effectiveness of limited resection in patients with lung cancer by analyzing their locally disease-free survival rates at 5 and 10 years. RESULTS Of 179 patients enrolled between 1997 and 2002, 90 were male and 89 female. They were divided into 77 GGO types and 102 solid types. During surgery, conversions from limited resections to standard operations were performed on six patients to avoid the risk of local-regional recurrence. Finally, WWR was performed on 73 patients, segmentectomy on 26 and lobectomy on 80, respectively. There were 138 lung cancers and 41 non-cancers. Of 138 cancer patients, 114 patients are alive and 24 died. There were no local-regional recurrences among the 58 cancer patients who underwent limited resection. CONCLUSIONS This intermediate-term outcome suggests that the selection of the type for lung resection using this management algorithm for small peripheral lung lesions was effective for preventing both local-regional recurrences and the excessive resection of normal lung tissue.

Outcome of surgical resection for recurrent pulmonary metastasis from colorectal carcinoma.

BACKGROUND The outcomes after repeat pulmonary resection for colorectal cancer (CRC) and the factors associated with the prognosis of these patients remain uncharacterized. METHODS Data on 156 patients who underwent curative resection of pulmonary metastasis from CRC were reviewed. Repeat pulmonary resection was performed in 25 patients; the present study examined the outcomes and factors associated with prognosis after repeat pulmonary resection. RESULTS The 5-year survival rate after the first pulmonary resection was 56.2%. A multivariate analysis identified a histological type other than well-differentiated adenocarcinoma, a high prethoracotomy serum carcinoembryonic antigen (CEA) level, and the presence of hilar or mediastinal lymph node metastasis as poor prognostic factors for the first pulmonary resection. The 5-year survival rate after repeat pulmonary resection was 42.1%. Hilar or mediastinal lymph node metastasis at the time of the repeat resection was significantly associated with poor survival. CONCLUSIONS Repeat pulmonary resection for metastatic CRC provides satisfactory outcomes. Hilar or mediastinal lymph node involvement is consistently associated with a poor prognosis after the first and repeat pulmonary resections.

Innate immune therapy with a Bacillus Calmette-Guérin cell wall skeleton after radical surgery for non-small cell lung cancer: A case-control study

PurposeWe investigated whether adjuvant immunotherapy with Bacillus Calmette-Guérin (BCG) cell wall skeleton (CWS) and surgical resection was better than resection, with or without other adjuvant therapy, for patients with non-small cell lung cancer (NSCLC).MethodsThe case group comprised 71 patients who underwent radical surgery for NSCLC, followed by BCG-CWS immunotherapy, with follow-up data available. The case-control study was designed with one control selected for each case-group patient. Each control was matched by pathological stage and year of birth (±5 years). BCG-CWS 200 μg was inoculated intracutaneously in the upper arm four times per week (sensitization phase); then at 4-week intervals (therapeutic phase).ResultsThe case-group patients received 45 ± 22.6 (average ± SD) cycles of BCG-CWS inoculation. Overall 5-year and 10-year survival rates were 71% and 61% for the case-group patients, and 63% and 43% for the control-group patients. The survival rate of the case group was better than that of the control group (not significant; P = 0.114). The same trend was seen in the patients with stage III or N+ NSCLC (not significant; P = 0.114, P = 0.168). There were no life-threatening adverse events.ConclusionsBCG-CWS immunotherapy seemed to improve survival after resection of NSCLC, especially locally advanced NSCLC. Moreover, this immunotherapy did not compromise quality of life during treatment.

Prognostic factors for gefitinib-treated postoperative recurrence in non-small cell lung cancer.

Background and Objectives: The association between epidermal growth factor receptor (EGFR) mutations and response to EGFR tyrosine kinase inhibitor (TKI) has been consistently confirmed in a number of studies. However, it is still unclear whether a response to TKI treatment translates into increased survival for patients with non-small cell lung cancer (NSCLC). Methods: EGFR mutations were analyzed in 169 primary lung cancer tissues by RT-PCR and sequencing of multiple clones. The association between EGFR mutation status and the clinical outcome of gefitinib treatment was investigated. For mutation-positive cases, the percentage of mutated clones from the total number of clones was calculated. This ratio was used as the quantitative index of EGFR mutations. Results: We identified mutations in 71 of 169 patients with NSCLC. 46 patients were treated with gefitinib for postoperative recurrence. Progression-free survival and overall survival after initial gefitinib were significantly longer in patients with mutation than with wild type (univariate analysis, p < 0.001 for both). Multivariate analyses identified EGFR mutations and longer disease-free intervals after surgery as significant prognostic factors for survival. By quantitative analysis of mutation-positive cases, the increased ratio of mutated EGFR transcripts significantly associated with longer survival after gefitinib. Conclusions: EGFR mutation status and disease-free interval were associated with prolonged progression-free survival and overall survival after gefitinib treatment for postoperative recurrence of NSCLC. Quantitative analysis of mutated EGFR transcripts provided additional information for the stratification of patients with mutated EGFR.

Prognostic value of intraoperative pleural lavage cytology for lung cancer without carcinomatous pleuritis: importance in patients with early stage disease during long-term follow-up.

PURPOSE The clinical significance of intraoperative pleural lavage cytology (PLC) for lung cancer has been insufficiently elucidated. We therefore reviewed the surgical results of lung cancer patients without carcinomatous pleuritis followed up over the long term to elucidate PLC implications. PATIENTS AND METHODS PLC was performed immediately after thoracotomy in consecutive lung cancer patients without carcinomatous pleuritis undergoing tumor resection between 1988 and 1997. Postoperative follow-up was generally performed for at least 5 years while checking tumor recurrence and survival. RESULTS Eighty-nine (13.1%) of 679 patients had positive PLC findings, which were observed more frequently in patients with advanced stage, larger tumor size, higher involvement of the pleura, lymph node, lymphatics and vessels. The overall 5- and 10-year survival rates in PLC-positive patients were 43% and 25%, respectively, while those in PLC-negative patients were 66% and 58%, respectively (p<0.0001). Among 395 patients with stage I disease, 35 (8.9%) showed PLC-positive findings, and their overall survival rate was significantly poor compared with those with PLC-negative findings (p<0.0001). In contrast, such differences were not observed among patients with more advanced stage diseases. In regard to histological type, a difference in the postoperative survival rate according to PLC status was statistically found in adenocarcinoma type (p<0.0001), but not in squamous cell carcinoma type (p=0.24). According to multivariate analysis, PLC was an independent prognostic factor for all tested patients (p=0.007, hazard ratio=0.60) as well as for those with stage I disease (p=0.0135, hazard ratio=0.51). When examining postoperative pleural recurrence, the rate for PLC-positive patients was statistically higher than that for PLC-negative patients (p<0.0001, hazard ratio=0.08). Interestingly, late pleural recurrence more than 5 years occurred in five (5.6%) of PLC-positive patients, all of whom were included in stage I. CONCLUSIONS Based on the present analysis of long-term follow-up after operation, PLC may also be an independent prognostic factor. In particular, the PLC status of patients with stage I disease or adenocarcinoma type has an important impact on survival. PLC-positive findings may be a high risk for postoperative pleural recurrence. For PLC-positive patients with stage I disease, careful serial follow-up for more than 5 years is required while paying attention to late pleural recurrence.

Improved Diagnostic Efficacy by Rapid Cytology Test in Fluoroscopy-Guided Bronchoscopy

Background: Fluoroscopy-guided bronchoscopy is a safe and routine method used to obtain a histologic or cytologic specimen of peripheral lung nodules, but it has low sensitivity in diagnosing malignant tumors. Although feedback from rapid cytology tests are expected to improve diagnostic rates, the value of the routine use of rapid cytology tests has not been established. Materials and Methods: We prospectively studied 657 patients with suspected peripheral malignant lung lesions on chest computed tomography who underwent fluoroscopy-guided bronchoscopy between January 2002 and December 2004. Rapid on-site cytopathologic examinations (ROSE) were performed during bronchoscopic examinations. The additional approach to the lesions was performed immediately after conventional bronchoscopic examinations when ROSE was not considered diagnostic. Results: There were 528 patients diagnosed as having malignant lesions. In 477 of these patients (90.3%), final malignant diagnosis was established by the initial bronchoscopy. Among these, 84 patients (15.9%) were diagnosed only with the additional feedback from ROSE. Of 240 peripheral lesions ≤2 cm, 174 were found to be malignant. Without ROSE, 110 (63.2%) of peripheral malignant lesions were diagnosed by bronchoscopy. The integration of ROSE enabled us to diagnose an additional 40 patients (23.0%) by bronchoscopy. ROSE improved diagnostic yield independent of the site and histology of the lesions and experience of the operators. Conclusion: ROSE increased the diagnostic yield of bronchoscopy from 74.4% to 90.3% and therefore is an effective reinforcement in bronchoscopic diagnosis of peripheral pulmonary malignancies. The use of ROSE in routine bronchoscopy should be encouraged.

Metastatic Tumor Doubling Time Is an Independent Predictor of Intrapulmonary Recurrence after Pulmonary Resection of Solitary Pulmonary Metastasis from Colorectal Cancer

Background: Several investigators have previously reported the prognostic factors affecting survival after a surgical resection of pulmonary metastasis from colorectal cancer (CRC). However, there have so far been no reports describing prognostic factors related to the tumor doubling time (TDT) of pulmonary metastasis. Methods: 65 patients with solitary pulmonary metastasis from CRC were retrospectively reviewed and the prognostic factors after pulmonary resection including TDT were analyzed. Results: The 5-year intrapulmonary recurrence-free survival rates after pulmonary resection was 59.9%. The TDT of pulmonary metastasis (<100 vs. 100 days or higher) was only a significant prognostic factor in intrapulmonary recurrence after the pulmonary resection (p = 0.0006). The 5-year overall survival rate after the pulmonary resection was 64.2%. Preoperative serum carcinoembryonic antigen (CEA) level (<5 vs. 5 ng/ml or higher) was the only significant prognostic factor in overall survival after the pulmonary resection (p = 0.0049). The overall survival of patients whose TDT was 100 days or higher tended to be better than that of patients whose TDT was <100 (p = 0.0631). Conclusions: The TDT of solitary pulmonary metastasis is a significant prognostic factor after surgery for solitary pulmonary metastasis from CRC.

Surgical management of primary intrathoracic goiters

Intrathoracic goiters account for 3.1%–5.8% of all mediastinal masses. Primary intrathoracic goiters, which receive their blood supply from mediastinal vessels and disconnect at the cervical thyroid, are even rarer. This report presents two cases of surgical resection of benign and malignant primary intrathoracic goiters. Usefulness of a whole-body 18F-fluorine-2-fluoro-d-glucose positron emission tomography/computed tomography study and intraoperative fine-needle aspiration cytology in the management of primary intrathoracic goiters is discussed.

Malignant pleural mesothelioma with long-term tumor disappearance of a local relapse after surgery: a case report.

IntroductionThere have been few reports of spontaneous regression of malignant pleural mesothelioma, but the mechanism for this is unknown. We present a case report on a patient with malignant pleural mesothelioma showing apparent tumor disappearance in a local relapse after surgery.Case presentationA 73-year-old man presented with malignant pleural mesothelioma in the right thoracic cavity. A pleurectomy was performed, and as expected, the tumor locally relapsed with increasing chest pain. However, the symptoms suddenly improved while the tumor was apparently reduced, and spontaneous tumor regression was initially considered. The patient confessed that he had self-administered a mushroom extract with alternative parasympathetic nerve stimulation therapy thereafter. The complete disappearance of the tumor was clinically achieved during a 29-month follow-up with continuing self-treatment.ConclusionThis is the first report describing a malignant pleural mesothelioma patient in Japan showing long-term complete disappearance of a local relapse after surgery. This event was a tumor regression possibly due to an immunological effect of combined complementary and alternative therapy.

Pericardial effusion following pulmonary resection

OBJECTIVE Postoperative pericardial effusion commonly occurs after open heart surgery. However, after general thoracotomy such as pulmonary resection, there have been few reports of pericardial effusion. The purpose of this study is to investigate patients with pericardial effusion following pulmonary resection. METHODS Among 2,385 patients with pulmonary resection for lung neoplasm in our institute, eight patients, whose pericardium had never been opened during the operation, developed pericardial effusion. The clinical characteristics of the eight patients were analyzed. RESULTS Pericardial effusion after pulmonary resection was divided into two subtypes: pericardial effusion in three patients with left thoracotomy occurring within 30 days postoperatively, and pericardial effusion in the remaining five patients with right thoracotomy occurring more than 30 days postoperatively. Pericardiotomy or pericardiocentesis was performed in three symptomatic patients, and the remaining five asymptomatic patients were treated with diuretics. Pericardial effusion disappeared in three of the five patients about 1-3 months after the conservative treatment, while, in the remaining patients, because pericardial effusion had increased gradually, pericardiocentesis was performed. CONCLUSION From our experience, the treatment strategy of drainage for early pericardial effusion and diuretics for late pericardial effusion seems to be appropriate.