Sung Soo Chang

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.

A novel method for determining adjacent lung segments with infrared thoracoscopy.

OBJECTIVES We investigated a new technique for identifying the lung intersegmental line using infrared thoracoscopy with intravenous injection of indocyanine green. METHODS This was an experimental animal study, and target segments were established preoperatively. Six adult beagle dogs underwent thoracotomy. After the corresponding pulmonary artery of the target segment had been ligated, indocyanine green was administered intravenously during infrared thoracoscopy. The lung was separated into 2 areas, white and blue, according to the blood flow on the monitor. We marked the visceral pleura with electrocautery along the transition zone showing a change in color from blue to white. The experimental lung was removed and subjected to pathologic and radiologic analysis. RESULTS After injection of indocyanine green, infrared thoracoscopy showed that the area of normal perfusion changed to blue, whereas the area at which perfusion was absent remained white. The transition zone between colors was distinct, and the blue stain remained visible during the marking procedure. Three-dimensional computed tomographic analysis indicated that the marking separated the target segmental bronchus from the adjacent one. Detailed macroscopic and microscopic study confirmed that the marking corresponded to the intersegmental line. CONCLUSION By using infrared thoracoscopy with indocyanine green, it is possible to detect the intersegmental line without inflating the lung.

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.

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.

Clinical trial of new methods for identifying lung intersegmental borders using infrared thoracoscopy with indocyanine green: comparative analysis of 2- and 1-wavelength methods

OBJECTIVES Infrared thoracoscopy is a new method of identifying lung intersegmental borders. This study compared the efficacy of 2- and 1-wavelength infrared thoracoscopy. METHODS A total of 30 consecutive patients who underwent segmentectomy were evaluated by these methods (2-wavelength method, 10 patients; 1-wavelength method, 20 patients). We ligated the dominant pulmonary artery and then observed the lung using an infrared thoracoscope after indocyanine green (ICG) intravenous injection. The 2-wavelength infrared thoracoscope irradiation and detection were conducted at 940 and 805 nm, respectively, and the images were projected based on the difference of the two reflected wavelengths. ICG absorbs 805 nm wavelength light, and the ICG distribution area appears blue against a white background. On the other hand, the 1-wavelength infrared thoracoscope irradiation and detection were conducted at 780 and 830 nm, respectively. The area stained with ICG shows fluorescence. RESULTS In the 2-wavelength method, 3.0 mg/kg of ICG was administered, and a well-defined white-to-blue border was observed in 9 of 10 patients. The staining duration was 220 (interquartile range, 187-251) s. In the 1-wavelength method, 0.5 mg/kg of ICG was administered, and a well-defined border between areas with or without fluorescence was observed in 19 of 20 patients. The staining duration was 370 (interquartile range, 296-440) s, which was significantly longer than the staining duration with the 2-wavelength method (P = 0.0001). CONCLUSIONS Infrared thoracoscopy is useful for detection of intersegmental borders. The dose of ICG for the 1-wavelength method was less than that for 2-wavelength method, and the duration of staining was longer.

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.

Tracheal cartilage regeneration and new bone formation by slow release of bone morphogenetic protein (BMP)-2

We investigated the efficiency of bone morphogenetic protein (BMP)-2 released slowly from gelatin sponge for tracheal cartilage regeneration. A 1-cm gap was made in the mid-ventral portion of each of 10 consecutive tracheal cartilages. In the control group (n = 4), the resulting gap was left untreated. In the gelatin group (n = 4), plain gelatin was implanted in the gap. In the BMP-2 group (n = 4), gelatin containing 100 &mgr;g BMP-2 was implanted. We euthanatized all dogs in each group at 1, 3, 6, and 12 months after the implantation, respectively, and then examined the implant site macro- and microscopically. In the BMP-2 group, regenerated fibrous cartilage and newly formed bone were observed at 1 and 12 months. Regenerated cartilage was observed at the ends of the host cartilage stumps, with newly formed bone in the middle portion. The gaps were filled with regenerated cartilage and newly formed bone. At 3 and 6 months, regenerated cartilage, but not newly formed bone, was evident. The regenerated cartilage was covered with perichondrium and showed continuity with the host cartilage. We succeeded in inducing cartilage regeneration and new bone formation in canine trachea by slow release of 100 &mgr;g BMP-2 from gelatin.

Clinical trial of video-assisted thoracoscopic segmentectomy using infrared thoracoscopy with indocyanine green.

OBJECTIVES The maintenance of a good surgical view is mandatory in video-assisted thoracoscopic surgery (VATS). For routine segmentectomy, it is necessary to re-inflate the lung in order to identify the intersegmental line. However, such re-inflation can occasionally obstruct the surgical view. Infrared thoracoscopy (IRT) with indocyanine green (ICG) can reveal the intersegmental line based on blood flow differences, without the need for lung re-inflation. The purpose of this study was to confirm the usefulness of IRT with ICG for VATS. METHODS Between October 2008 and September 2011, 44 consecutive patients underwent segmentectomy at our institution. In 13 patients, VATS segmentectomy using IRT with ICG was employed. Informed consent was obtained from all patients. Computed tomography was performed to identify the dominant pulmonary artery supplying the target segment. The operations were performed using two ports and one mini-thoracotomy (3-6 cm). The dominant arteries were interrupted, and the intersegmental line was identified using IRT with ICG. RESULTS Identification of the intersegmental line was possible in 11 (84.6%) of the 13 patients. The average age was 70 years, and 6 of the patients were male. The mean operation time was 191 min, and the mean bleeding volume was 64 ml. The operation time and bleeding volume were similar to the values in the other 31 patients who underwent thoracotomy (167 min/115 ml, P = 0.212/0.361, respectively). No complications attributable to IRT with ICG were observed. CONCLUSIONS VATS segmentectomy using IRT with ICG allows the maintenance of a clear surgical view and identification of the intersegmental line in a high proportion of cases. Therefore, we consider this method to be useful for minimally invasive thoracic surgery.

Prognostic factors in patients after lobectomy for p-T1aN0M0 adenocarcinoma

OBJECTIVES The seventh edition of the TNM Classification of Malignant Tumours was published in 2009. This study was conducted to investigate the prognostic factors of p-T1aN0M0 pulmonary adenocarcinoma, which is the earliest stage defined in the new TNM classification. METHODS We retrospectively studied 122 patients who underwent lobectomy at our institution for p-T1aN0M0 adenocarcinoma, as re-categorized in the seventh TNM classification. The patients were separated into groups on the basis of the following clinicopathologic parameters: age, < 70 vs. > 70 years; gender, male vs. female; preoperative serum carcinoembryonic antigen (CEA) level, < 5.0 vs. ≥ 5.0 ng/dl; tumour size, <10 vs. >10 mm; intratumoral vascular or lymphatic invasion, positive vs. negative. Univariate and multivariate analyses of disease-free survival were performed. RESULTS The median follow-up period was 41.4 months. Univariate analysis showed that prognostic factors such as age, CEA elevation and intratumoral vascular or lymphatic invasion were significant (age, < 70 vs. > 70 years; 97.1% vs. 82.0%, P = 0.0027; preoperative serum CEA level, < 5.0 vs. > 5.0 ng/dl; 93.3% vs. 33.3%, P < 0.0001; intratumoral vascular or lymphatic invasion, positive vs. negative; 31.3% vs. 96.5%, P < 0.0001). Multivariate analysis demonstrated that only intratumoral vascular or lymphatic invasion was a significantly independent prognostic factor (P = 0.0039, Hazard Ratio, 0.066; 95% Confidence Interval, 0.011-0.419). CONCLUSIONS Intratumoral vascular or lymphatic invasion should always be studied and included in the final pathology report in order to consider potential clinical and therapeutic relevance. The efficacy of adjuvant chemotherapy for these patients should also be evaluated in clinical trials.