Hitoshi Igai

Evaluation of the new TNM staging system proposed by the International Association for the Study of Lung Cancer at a single institution

OBJECTIVE The seventh TNM Classification of Malignant Tumours will be published in 2009. The International Association for the Study of Lung Cancer has proposed a revision of the current pathologic staging system. We illustrated the effects of this new system and pointed out potential problems using a retrospective study of surgical cases of non-small cell lung cancer at our institution. METHODS Subjects were 1532 patients for whom current pathologic staging was possible. These data were migrated into the new staging system. The numbers of patients at various stages determined by using the current and new staging systems were, respectively, as follows: IA (n = 700, n = 700), IB (n = 338, n = 249), IIA (n = 49, n = 164), IIB (n = 129, n = 116), IIIA (n = 204, n = 234), IIIB (n = 77, n = 17), and IV (n = 35, n = 52). Prognoses were compared by using the current and the new systems. RESULTS By using the new staging system, 5-year survivals by T classifications were as follows: T1a, 82.6%; T1b, 73.3%; T2a, 63.5%; T2b, 50.1%; T3, 40.6%; and T4, 34.6%. There were significant differences between the new T1a and T1b (P = .0026), T1b and T2a (P = .0027), and T2a and T2b (P = .0062) classifications. In the current system 5-year survivals based on pathologic stages were as follows: IA, 84.8%; IB, 72.9%; IIA, 53.8%; IIB, 53.7%; IIIA, 31.8%; IIIB, 34.0%; and IV, 27.1%. There were significant differences between stages IA and IB (P < .0001) and stages IIB and IIIA (P = .0006). In the new system these were as follows: IA, 84.8%; IB, 75.2%; IIA, 62.4%; IIB, 52.1%; IIIA, 32.4%; IIIB, 15.2%; and IV, 30.6%. There were significant differences between stages IA and IB (P = .0004), IB and IIA (P = .0195), IIA and IIB (P = .0257), IIB and IIIA (P = .0040), and IIIA and IIIB (P = .0399). CONCLUSION Although the outcomes for stages IIIB and IV were reversed, the new pathologic staging system was considered valid based on our single-institution evaluation.

Postrecurrence survival in patients with stage I non-small cell lung cancer

OBJECTIVE Postoperative recurrence is a major obstacle to achieving a cure and long-term survival in patients with non-small lung cancer. However, prognostic factors and the efficacy of therapy after recurrence remain controversial. We evaluated the clinical outcomes of patients with resected lung cancer for postrecurrence prognostic factors. METHODS Patients who underwent complete resection with systematic lymph node dissection for stage I non-small cell lung cancer were selected. Cases of low-grade malignancy, preoperative therapy, history of previous malignancy or death within 30 days of operation were excluded. A total of 397 patients were retrospectively reviewed. RESULTS Out of 87 patients who had recurrence after surgery, 45 had symptoms at the initial recurrence. The initial recurrent site was local in 30 patients and distant in 57. Single-site recurrence was detected in 48 patients and multiple-site recurrence was seen in 39. The recurrent site was the ipsilateral thorax in 49 patients, the contralateral thorax in 32, the cervico-mediastinum in 15, brain in 12 and bone in 11. Surgery was performed in 20 patients, whereas non-surgical therapy was performed in 55 (chemotherapy, 16; radiation therapy, 33; chemo-radiation therapy, 6). Prognostic analysis of factors related to recurrent status demonstrated that symptoms at the initial recurrence, cervico-mediastinal metastasis, liver metastasis and postrecurrence therapy were significant prognostic factors in both univariate and multivariate analysis. CONCLUSIONS Symptoms at the initial recurrence, cervico-mediastinal metastasis and liver metastasis were worse prognostic factors after recurrence. Postrecurrence therapy for the initial recurrence may prolong survival after recurrence.

New clinically applicable method for visualizing adjacent lung segments using an infrared thoracoscopy system

OBJECTIVE Our objective was to attempt a clinical trial of segmentectomy using the infrared thoracoscopy system after intravenous injection of indocyanine green. PATIENTS AND METHODS A total of 8 patients with lung lesions were investigated (5 with primary lung cancer, 2 with metastatic lung tumor, and 1 with inflammatory change). All were scheduled to undergo segmentectomy and had been confirmed to have no allergy to iodine or indocyanine green. Informed consent was obtained from all patients. We identified the dominant pulmonary artery supplying the target segment using reconstructed computed tomography images. The dominant pulmonary artery of the target segment was ligated, and after we had observed the lung using the infrared thoracoscopy system after intravenous injection of indocyanine green (3.0 mg/kg), and marked the white-to-blue transitional zone by electrocautery, we performed segmentectomy. RESULTS Average operation time was 150 ± 62.1 minutes, and bleeding volume was 68.8 ± 30.5 mL. Under infrared thoracoscopy, the area with a normal blood supply became stained blue 13 seconds after injection of indocyanine green. Maximum staining intensity was attained 28 seconds after dye injection, and the observation duration was 3.5 minutes. A well-defined color zonation was observed in all patients. We had enough time to mark it. No complications attributable to infrared thoracoscopy after intravenous injection of indocyanine green were encountered. CONCLUSIONS Infrared thoracoscopy with indocyanine green makes it possible to identify the target lung segment easily and quickly without the need for inflation. This method will be especially useful for cases associated with severe emphysema or when surgery offers a limited view, as is the case with video-assisted thoracic surgery.

Regeneration of canine tracheal cartilage by slow release of basic fibroblast growth factor from gelatin sponge

We investigated the efficiency of basic fibroblast growth factor (b-FGF) released from a gelatin sponge in the regeneration of tracheal cartilage. A 1-cm gap was made in the midventral portion of each of 10 consecutive cervical tracheal cartilages (rings 4 to 13) in 15 experimental dogs. In the control group (n = 5), the resulting gap was left blank. In the gelatin group (n = 5), a gelatin sponge alone was implanted in the gap. In the b-FGF group (n = 5), a gelatin sponge containing 100 &mgr;g b-FGF solution was implanted in the gap. We euthanatized one of the five dogs in each group at 1 month after implantation and one at 3 months and examined the implant sites macroscopically and microscopically. In the control and gelatin groups, no regenerated cartilage was observed in the tracheal cartilage gap at 1 or 3 months. The distances between the cartilage stumps had shrunk. In the b-FGF group, fibrous cartilage had started to regenerate from both host cartilage stumps at 1 month. At 3 months, regenerated fibrous cartilage filled the gap and had connected each of the stumps. The regenerated cartilage was covered with regenerated perichondrium originating from the host perichondrium. Shrinkage of the distance between the host cartilage stumps was not observed in the b-FGF group. We succeeded in inducing cartilage regeneration in the gaps in canine tracheal cartilage rings by using the slow release of b-FGF from a gelatin sponge. The regenerated cartilage induced by b-FGF was fibrous cartilage.

Video-assisted thoracic lobectomy with bronchoplasty for lung cancer, with special reference to methodology.

Few studies have described video-assisted thoracic surgery (VATS) to bronchoplasty with pulmonary resection. Here, we report the successful implementation of VATS bronchoplasty, as determined retrospectively. Between 2005 and 2010, 362 patients underwent elective lung resection for malignant or benign lung tumors. Of these patients, VATS lobectomy with bronchoplasty was performed in seven patients (four men, three women; median age, 72.9 years). The medical records were retrospectively reviewed. Of the seven patients, six had primary lung cancer (PLC), and one had metastatic cancer of the lung. The surgical procedures were lobectomy with wedge bronchoplasty. The patients with PLC also underwent mediastinal or hilar lymph node dissection. The median total operating time was 230 min, and the median blood loss was 152 ml. The median postoperative hospital stay was seven days, without major postoperative complications. The most important feature of the described method is that the surgeon mainly observes the operative field directly, through a working wound; the surgical team observes via a monitor. An advantage for the surgeon is the ability to use the same instruments in VATS as are used in conventional thoracotomy, as well as the same suturing techniques in vascular reconstruction, especially involving the pulmonary artery.

Usefulness of [18F]fluoro-2-deoxy-D-glucose positron emission tomography for predicting the World Health Organization malignancy grade of thymic epithelial tumors

OBJECTIVE The objective of this study was to investigate whether the maximum standardized uptake value (SUVmax) determined using positron emission tomography with [(18)F]fluoro-2-deoxy-D-glucose ((18)FDG-PET) can predict the grade of malignancy of thymic epithelial tumors based on the World Health Organization (WHO) classification. METHODS We retrospectively analyzed 13 patients with thymic epithelial tumors, who underwent (18)FDG-PET examination before treatment. The patients were subdivided into a thymoma group and a thymic carcinoma group, and the two were compared clinicopathologically. RESULTS There were six men and seven women, ranging in age from 36 to 78 years (mean, 58.8 ± 13.3 years). Mean tumor size was 47.3 ± 26.0mm, and the WHO classification was type A in two patients, type AB in none, type B1 in one, type B2 in three, type B3 in two, and thymic carcinoma in five. Thus, eight patients had thymoma and five had thymic carcinoma. The Masaoka stage was I in four patients, II in four, III in three, and IV in two. Mean pre-treatment SUVmax for the tumors overall was 5.24 ± 3.10, with a range of 1.73-11.21. Mean SUVmax in the thymic carcinoma group was 8.15 ± 7.88, and that in the thymoma group was 3.43 ± 2.19, the difference being significant (P = 0.002). CONCLUSIONS A significant relationship was observed between SUVmax and morphological classification by the WHO system for this cohort of thymic epithelial tumors. Pre-treatment SUVmax may be useful for differentiating thymoma from thymic carcinoma.

Surgical treatment for non-small cell lung cancer in octogenarians--the usefulness of video-assisted thoracic surgery.

The purpose of this study was to investigate whether surgical treatment for non-small cell lung cancer (NSCLC) confers a survival benefit in octogenarians, and whether video-assisted thoracic surgery (VATS) is effective in terms of postoperative morbidity, mortality, and quality of life (QOL). Among 1684 patients with primary NSCLC who underwent pathologically complete resection, 95 were octogenarians. Operation was performed by the VATS approach (VATS group, n=58) or the standard thoracotomy (ST group, n=37). Although postoperative cardiopulmonary complications occurred in 20 cases (21.1%), all were manageable. In the ST group cardiopulmonary complications occurred more frequently than in the VATS group (P=0.030). The overall 5-year survival rate of the 95 octogenarians, including deaths from all causes, was 54.4%. The overall 5-year survival rate of patients with stage IA disease was 65.2%. These outcome data were not significantly worse than those for patients aged 79 years or under (P=0.136). There was no significant difference in overall 5-year survival rates between the ST group and the VATS group (P=0.144). The VATS approach for pulmonary resection is recommended for octogenarians with NSCLC. Surgical resection is the optimal treatment for stage IA NSCLC, and therefore, advanced age is not a contraindication for curative resection.

Rapidly expanding extrapleural hematoma

We present a rare case of extrapleural hematoma due to chest trauma in an anticoagulated male patient. Chest computed tomography revealed multiple left rib fractures and a D-shaped opacity in the upper left side of the thorax suggesting extrapleural hematoma, which was caused from continuous bleeding. His past history included alcoholic liver cirrhosis, which caused thrombocytopenia and coagulopathy. Therefore, the hematoma was expanding, causing circulatory and ventilatory disturbance and severe anemia despite the difficulty of expanding in the extrapleural space. As the bleeding did not stop, even after intercostal artery angiography with embolization was performed, surgical treatment was undertaken to control the bleeding and evacuate the huge hematoma. The problems associated with the diagnosis and treatment of an extrapleural hematoma are discussed in the light of this case.

Clinicopathological study of p-T1aN0M0 non-small-cell lung cancer, as defined in the seventh edition of the TNM classification of malignant tumors

OBJECTIVE The seventh edition of the TNM Classification of Malignant Tumours was published in 2009. The present study was conducted to investigate the clinicopathological features of p-T1aN0M0 non-small-cell lung cancer, which is the earliest stage defined in the new tumor, node, metastasis (TNM) classification, in relation to patient prognosis. METHODS We retrospectively studied 162 patients, who underwent surgical resection at our institution for p-T1aN0M0 non-small-cell lung cancer, as re-categorized in the seventh TNM classification. Univariate and multivariate analyses of disease-free survival were performed. RESULTS The mean tumor size was 13.2 ± 4.7 mm. The maximum tumor diameter was >10 mm in 104 cases (64.6%), and ≤ 10 mm in 58 (35.4%). The median follow-up period was 44.5 months. Univariate analysis showed that the 5-year disease-free survival rate of patients with and without preoperative serum carcinoembryonic antigen elevation was 50.8% and 95.1% (P<0.0001), respectively, that of patients with and without blood vessel or lymphatic invasion was 40.0% and 95.8% (positive vs negative, P<0.0001), respectively, and that of patients aged ≥ 70 years and <70 years was 86.8% and 96.1% (P=0.014), respectively. Multivariate analysis including these three clinicopathologic factors demonstrated that preoperative elevation of the carcinoembryonic antigen level and blood vessel or lymphatic invasion were independent prognostic factors. CONCLUSION In patients with p-T1aN0M0 non-small-cell lung cancer, an elevated preoperative carcinoembryonic antigen level and blood vessel or lymphatic invasion tend to affect prognosis to a greater degree than tumor size. Therefore, the efficacy of adjuvant chemotherapy for these patients should be evaluated in clinical trials.

Widespread and Early Tracheal Cartilage Regeneration by Synchronous Slow Release of b-fgf and Bmp-2

Our previous studies have demonstrated that slow release of basic fibroblast growth factor (b-FGF) or bone morphogenetic protein 2 (BMP-2) induces cartilage regeneration. In the present study, we investigated whether synchronous slow release of b-FGF and BMP-2 would induce more widespread and earlier cartilage regeneration than that induced by each growth factor alone. A 1-cm defect was made in the mid-ventral portion of each of 10 consecutive tracheal rings. In four controls, the defect was left untreated. In the gelatin group (n = 4), empty gelatin sponge was implanted. In the b-FGF + BMP-2 group (n = 5), two gelatin sponges containing 100 &mgr;g of b-FGF or BMP-2 solution were implanted. After various periods, we euthanatized the dogs, and examined the implant sites. In the b-FGF + BMP-2 group, regenerated fibrous cartilage connected the host cartilage stumps and completely filled the defect between them at 1, 2, 3, and 12 months. Regenerated cartilage was covered by regenerated perichondrium originating from the host perichondrium, and showed neovascularization in the extracellular matrix. We succeeded in inducing more widespread and earlier cartilage regeneration using synchronous slow release of b-FGF and BMP-2 than that induced by release of each growth factor alone.