Simple palliative mediastinal tracheostomy.

We describe a simple palliative mediastinal tracheostomy procedure in 3 patients with respiratory deficiency resulting from cervical tracheal stenosis caused by unresectable advanced tumors. A hole in the "apron" skin flap was anastomosed to the tracheostomy in the unaffected upper mediastinal trachea after partial resection of the manubrium and clavicle head. Simple palliative mediastinal tracheostomy helps to improve performance status by relieving respiratory deficiency or prolonged oroendotracheal intubation in patients with cervical tracheal stenosis caused by advanced tumors.

Phase II study of pemetrexed as first-line treatment in elderly (≥75) non-squamous non-small-cell lung cancer: Kyoto Thoracic Oncology Research Group Trial 0901.

BACKGROUND: Single-agent chemotherapy with third-generation non-platinum agents, such as docetaxel, vinorelbine, is a standard therapeutic option for elderly patients with non-small-cell lung cancer (NSCLC). Subset analysis of a previous phase III study comparing pemetrexed with docetaxel in the second-line setting showed the superiority of pemetrexed in an elderly (≥70) population in both efficacy and toxicity. PATIENTS AND METHODS: This was a single-arm phase II study of pemetrexed in elderly (≥75) Japanese patients with advanced non-squamous NSCLC. Patients received four cycles of pemetrexed (500 mg/m(2)) every 3 weeks. The primary endpoint was the response rate, and secondary endpoints were safety and survival. RESULTS: Twenty-eight patients were enrolled between January 2010 and April 2012. The median age of the patients was 77 years (range 75-88). All but one patient had adenocarcinoma histology. The median number of chemotherapy cycles administered was 4 (range, 1-12). Seventeen (60 %) patients completed four cycles of chemotherapy. Partial response was achieved in 7 patients (response rate: 25 %) and stable disease in 11 patients (disease control rate: 64 %). Median progression-free survival and overall survival were 3.3 and 17.5 months, respectively. Grade 3/4 neutropenia and thrombocytopenia were observed in 8 patients (29 %) and 2 (7 %), respectively. Non-hematologic toxicities were generally mild, and there were no treatment-related deaths. CONCLUSIONS: Although this study did not meet our primary endpoint, pemetrexed showed favorable antitumor activity with mild toxicity in elderly patients with non-squamous NSCLC. Further investigations of pemetrexed in this population are warranted (UMIN-CTR number, 000002452).

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.

Dual time point FDG PET for evaluation of malignant pleural mesothelioma.

OBJECTIVE: To evaluate whether 2-deoxy-2-18F-fluoro-D-glucose (FDG) positron emission tomography (PET) is more useful in differentiating malignant from benign pleural lesions, and whether delayed FDG PET imaging can improve the diagnostic performance in patients with suspicion of malignant pleural mesothelioma (MPM). METHODS: Thirty-three patients who were suspected of having MPM were examined with FDG PET. PET imaging (whole body) was performed at 60 min (early) post-FDG injection and repeated at 120 min (delayed) after injection only in the thoracic region. We evaluated the FDG uptake visually and semiquantitatively. The semiquantitative analysis using the standardized uptake value (SUV) was determined for both early and delayed images (SUVearly and SUVdelayed, respectively). RESULTS: The final diagnosis was MPM in 17 patients and benign pleural disease in 16 patients. The sensitivity, specificity, and accuracy to detect MPM on both early and delayed PET were all 88%. The mean value of SUVdelayed in MPM was significantly higher than that of SUVearly (P < 0.001). The mean values of SUVearly and SUVdelayed in MPM were significantly higher than the corresponding values in benign pleural disease (P < 0.01, respectively). CONCLUSION: FDG PET seems to be a useful imaging modality for differential diagnosis of MPM. In addition, the diagnostic performance on delayed PET was the same as that on early PET, although SUVdelayed was significantly higher than SUVearly in patients with MPM.

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 microg 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.

Reconstruction of emphysematous lung tissue using slowly released basic fibroblast growth factor from gelatin microspheres.

Basic fibroblast growth factor (bFGF) has a variety of activities including regeneration and neovascularization. This study was an attempt to reconstruct emphysematous lung tissue employing slow release of bFGF. Twenty beagle dogs were randomly split into four groups: a) control group (n = 5), b) porcine pancreatic elastase (PPE)-induced emphysema group (n = 5), c) FGF-MS group [n = 5, a suspension of bFGF-incorporated gelatin microspheres (MS) was injected via the pulmonary artery of emphysema model animals], and d) MS group (n = 5, MS without bFGF were injected). Four weeks after injection, the treated lungs were observed histologically, and the mean linear intercept (Lm) was calculated in each group. Lm in the FGF-MS and MS groups was significantly smaller than that in the emphysema group (p < 0.0001), and the size of the dilated alveoli was similar to that in the control group. These changes were more evident in the FGF-MS group, where almost normal alveoli and dense microvascularization were observed around the small pulmonary arteries. Reconstruction of emphysematous lungs was achieved by intrapulmonary arterial administration of MS with or without bFGF. This method may allow trans-pulmonary arterial therapy for pulmonary emphysema.

Closure of the pleural dead space after pneumonectomy in a rabbit model: use of bioabsorbable lactic acid and caprolactone copolymer cubes.

The remaining pleural dead space after pulmonary resection sometimes causes serious complications, such as empyema. The objective of this study was induction of granulation tissue in uninfected pleural space after pneumonectomy in a rabbit model using implantation of bioabsorbable and porous poly-l-lactic acid and epsilon-caprolactone copolymer (PLAC) cubes. Twelve Japanese white rabbits were randomly split into two groups: the control group (n = 6) underwent simple left pneumonectomy, whereas the experimental group (n = 6) underwent left pneumonectomy followed by filling of the left hemithorax with PLAC cubes. One rabbit in each group was killed at 1, 2, 3, and 6 months after surgery, and pleural tissue was evaluated. In the experimental group, granulation tissue inside the PLAC cubes had begun to form at 1 month after implantation. From 3 months to 6 months, proliferated granulation tissue occupied the left postpneumonectomy pleural space with no residual space. The implanted PLAC material was being gradually degraded. We were able to induce self-assembled granulation tissue in the pleural space after pneumonectomy in a rabbit model using bioabsorbable PLAC cubes. The use of this technique allowed the residual pleural space to be closed after pulmonary resection.

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 microg 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 microg BMP-2 from gelatin.

Clinical application of infrared thoracoscopy to detect bullous or emphysematous lesions of the lung.

OBJECTIVE: We have previously reported that infrared thoracoscopy was useful in detecting emphysematous lesions in a canine model of lung emphysema. We applied infrared thoracoscopy to determine the feasibility and efficacy of planning bullectomy for patients with spontaneous pneumothorax. METHODS: A total of 8 patients with spontaneous pneumothorax were included in the study. No procedure-related complications were observed. Infrared thoracoscopy with a single injection of indocyanine green (3.0 mg/kg) was used to detect bullous lesions of the lung during surgical intervention. Partial lung resections of the bullous lesions were performed after image analysis based on color density data obtained by means of infrared thoracoscopy. RESULTS: Bullous or emphysematous lesions of the lung were demonstrated in white, whereas normal lung tissue was imaged in blue, under infrared thoracoscopy. We were able to detect small bullous lesions with infrared thoracoscopy because of its clearer visualization compared with thoracoscopy. Quantitative color-density analysis revealed a marked decrease of indocyanine green intensity, which reflected decreased blood flow of bullous lesions. All resected specimens were confirmed as bullous lesions based on microscopic examinations. CONCLUSION: Infrared thoracoscopy-guided lung resection is a safe and useful procedure in detecting small bullous lesions.

Intra-thoracic fibrous tissue induction by polylactic acid and epsilon-caprolactone copolymer cubes, with or without slow release of basic fibroblast growth factor.

OBJECTIVE: We investigated whether implantation of polylactic acid and epsilon-caprolactone copolymer (PLAC) cubes with or without basic fibroblast growth factor (b-FGF) released slowly from gelatin microspheres was able to induce fibrous tissue in the dead space remaining after pneumonectomy in the thoracic cavity. METHODS: Left pneumonectomy was performed in Japanese white rabbits. In the control group (n=6), the left thoracic cavity was closed without any treatment. In the FGF group (n=6), gelatin microspheres that released 100 microg of b-FGF were implanted into the left thoracic cavity. In the PLAC group (n=6), PLAC cubes were implanted into the left thoracic cavity. In the PLAC/FGF group (n=6), both PLAC cubes and gelatin microspheres releasing 100 microg of b-FGF were implanted into the left thoracic cavity. RESULTS: In the control and FGF groups, herniation of the heart, mediastinal shift, and overinflation of the right lung were observed. No granular tissue formation was observed. In the PLAC and PLAC/FGF groups, a dense area of newly formed soft tissue was observed, and only a mild mediastinal shift was observed during the 3-month follow-up period. Pathological examination revealed induction of fibrous and granular tissue in the left thoracic cavity. The foreign-body reaction induced by PLAC was very mild. CONCLUSIONS: Implantation of PLAC cubes with or without gelatin microspheres releasing 100 microg of b-FGF is able to induce fibrous tissue in the post-pneumonectomy dead space.

Tracheal cartilage regeneration by slow release of basic fibroblast growth factor from a gelatin sponge.

OBJECTIVE: We investigated whether implantation of a gelatin sponge, releasing basic fibroblast growth factor slowly (b-FGF) into a tracheal cartilage defect, would induce regeneration of autologous tracheal cartilage. METHODS: We created a 1-cm defect in the midventral portion of each of 10 consecutive cervical tracheal cartilage rings in 12 experimental dogs. In the control group (n = 4), the resulting defects were left untreated. In the gelatin group (n = 4), empty gelatin sponges were implanted in the defects. In the basic fibroblast growth factor group (n = 4), gelatin sponges incorporating 100 microg of b-FGF solution were implanted in the defects. We killed the 4 dogs in each group at 1, 3, 6, and 12 months after implantation, respectively, and examined the implant sites macro- and microscopically. RESULTS: In the control and gelatin groups, no regenerated cartilage was observed in the tracheal cartilage defects, and the width of the gap between the host cartilage stumps had shrunk. In the b-FGF group, regenerated cartilage was observed in all dogs. The proportion of the defect in the host cartilage occupied by regenerated cartilage was 13%, 84%, 75%, and 69% at 1, 3, 6, and 12 months, respectively. The regenerated cartilage was fibrous cartilage covered with perichondrium, which grew from the host perichondrium and showed continuity with the host cartilage stumps. CONCLUSIONS: Implantation of a gelatin sponge slowly releasing basic fibroblast growth factor induces tracheal cartilage regeneration, which subsequently fills a large proportion of experimentally created tracheal cartilage defects within 12 months after implantation.

Induction chemoradiotherapy (carboplatin-taxane and concurrent 50-Gy radiation) for bulky cN2, N3 non-small cell lung cancer.

OBJECTIVE: To improve the prognosis of cN2, N3 non-small cell lung cancer, we performed induction chemoradiotherapy (carboplatin-taxane chemotherapy and concurrent 50-Gy radiation) followed by surgery. METHODS: Patients with pathologically proven non-small cell lung cancer with bulky cN2, N3 disease were enrolled. Forty-one patients underwent an operation after chemoradiotherapy from January 2000 to April 2006. Either carboplatin-paclitaxel (n = 19) or carboplatin-docetaxel (n = 22) chemotherapy was randomly used. Two cycles of chemotherapy were performed with concurrent radiation (50 Gy). In all cases, conventional radiological reevaluations were performed; in the latest 21 cases, reevaluations with positron-emission tomography with fludeoxyglucose F 18 were also performed. RESULTS: In all 41 cases, complete resections were performed, with no operative mortality. The histologically complete response rate, major response rate, and minor response rate were 17.1% (7/41), 56.1% (23/41), and 26.8% (11/41), respectively. The 5-year overall survival was 52.7%. There were no differences in survival between taxane groups. Both the complete response and the major response groups revealed a significantly better 5-year survivals than the minor response group (85.7%, P = .044, 52.4%, P = .01). Even with persistent N2 disease, the 5-year survival in the major response group (66%) was promising. With the combination of conventional computed tomography and positron-emission tomography with fludeoxyglucose F 18 for reevaluation, eligible patients could be selected for this protocol. CONCLUSION: Surgery after chemoradiotherapy (carboplatin-taxane and 50-Gy radiation) for bulky cN2, N3 non-small cell lung cancer can be safely performed with promising results. Even with persistent N2 disease, the survival in the major response group was promising.

En bloc partial vertebrectomy for lung cancer invading the spine after induction chemoradiotherapy.

OBJECTIVE: The optimal surgical treatment for non-small cell lung cancer (NSCLC) with vertebral body invasion remains both controversial and challenging. We reviewed our experiences of NSCLC with vertebral body invasion, in which we have performed induction chemoradiotherapy followed by lung resection with en bloc partial vertebrectomy. METHODS: Six NSCLC patients with vertebral invasion underwent an operation following chemoradiotherapy from January 2001 to July 2006. Vertebral invasion was evaluated by the chest CT and MRI findings. Either carboplatin-paclitaxel (n=3) or carboplatin-docetaxel (n=3) was used. Two cycles of chemotherapy were performed with concurrent radiation (50 Gy) treatment. RESULTS: In all of the six cases, a complete resection with en bloc partial vertebrectomy was performed with no operative mortality. The histological complete response rate and major response rate were 16.7% (1/6) and 83.3% (5/6), respectively. The 5-year overall survival rate was 67.7%. In addition, no local failure was observed after surgery. CONCLUSIONS: Surgery after chemoradiotherapy (carboplatin/paclitaxel or docetaxel and 50 Gy radiation) for NSCLC with vertebral invasion could thus be performed with acceptable morbidity.

A surgical case of primary lung cancer with peripheral intrapulmonary lymph node metastasis.

We report on a case of a patient with lung adenocarcinoma and peripheral intrapulmonary lymph node (IPLN) metastasis who was misdiagnosed as having intrapulmonary metastasis. A subpleural nodular shadow visualized by radiography was diagnosed as an intrapulmonary metastasis originating from primary lung cancer. Preoperative evaluation indicated that this case was a clinical T4N1 lung adenocarcinoma with metastasis in the same lobe. However, postoperative evaluation showed that it was a peripheral IPLN metastasis, and this was actually a case of pathologic T2N1 adenocarcinoma. It may have been possible to treat this case non-surgically with the possibility of radical cure. This case suggests that a nodule is present in the same lobe with lung cancer, and it must be borne in mind that IPLN metastasis may be misdiagnosed as intrapulmonary metastasis.

Large cell carcinoma with neuroendocrine morphology of the lung.

We experienced a surgical case of large cell carcinoma with neuroendocrine morphology (LCCNM) of the lung. A 76-year-old man was admitted to our hospital because a routine chest X-ray examination had revealed a nodular shadow in the left lung field. 18F-fluorodeoxyglucose positron emission tomography showed accumulation of fluorodeoxyglucose in an area corresponding to the shadow. Transbronchial lung biopsy failed to give a definitive diagnosis, therefore open lung biopsy was performed because of suspected lung cancer. Needle biopsy was performed, and the tumor was diagnosed as large cell neuroendocrine carcinoma by rapid intraoperative pathological examination. As sampling of hilar lymph nodes revealed no metastasis, left upper segmentectomy was performed for severe obstructive pulmonary disease. Immunohistochemical examination finally diagnosed the tumor as LCCNM. The patient is doing well without recurrence at ten months after 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 mug 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.

Successful treatment for lung cancer associated with pulmonary sequestration.

We encountered a 69-year-old man with lung adenocarcinoma and pulmonary sequestration. The cancer lesion was located in the left upper lobe, with sequestration of the left lower lobe. Left upper lobectomy was performed after induction chemoradiotherapy, but the sequestered lung lobe was preserved because the preoperative respiratory function was poor. Preservation of the sequestered lung during surgery for lung cancer should be considered in patients who have poor respiratory function and no signs of respiratory infection.

Real time imaging and quantitative evaluation of the emphysematous lung by infrared thoracoscopy in experimental dogs.

To accurately excise emphysematous lung tissue in volume reduction surgery, we projected a digitally analyzed excision line on the real time image obtained by infrared thoracoscopy (IRT) with indocyanine green (ICG) intravenous injection. Emphysema was created in the canine lung by intrabronchial injection of elastase. We examined the emphysematous lung by IRT after intravenous injection of ICG. A digitized static image was obtained and analyzed in real time during the surgery. The color densities on the image were measured and the color density ratios (CDRs) calculated. We resected lung areas where the CDR was 1.0 or less. Resected and residual lung areas were examined microscopically. Microscopically, areas displayed as white by IRT with intravenous injection of ICG were emphysematous, and areas displayed as blue were normal. Areas with a CDR of 1.0 or less were emphysematous, and we were able to determine an appropriate excision line by connecting sample points with a CDR of 1.0. Use of digital image analysis combined with IRT after ICG injection enabled us to remove emphysematous regions accurately.

Successful treatment of massive bleeding into the open thoracotomy space by pulmonary artery occlusion: report of a case.

A 69-year-old man underwent decortication and latissimus dorsi muscle transposition for the treatment of chronic empyema in January 2001. The empyema recurred in March 2002, and open drainage was thus started in July 2002. In February 2003, massive hemorrhaging from the thoracic cavity occurred. Tamponade and hemostasis were performed immediately, and angiography revealed bleeding from the pulmonary artery (PA). After identification of the bleeding point, surgical hemostasis was successfully achieved following PA occlusion with a Swan-Ganz thermodilution catheter.

A combined small cell carcinoma of the lung containing three components: small cell, spindle cell and squamous cell carcinoma.

A 61-year-old man was referred to our hospital because of rapid growth of a mass shadow revealed by chest radiography. The mass was diagnosed as pure small cell carcinoma by CT-guided needle biopsy, and the patient underwent chemotherapy. However, as the tumor showed no response, we considered the possibility of some other form of malignancy and performed surgery. Postoperatively, the mass was diagnosed as small cell carcinoma combined with small cell, spindle cell and squamous cell carcinoma. We report this case in view of the rarity of this combination of morphologic patterns in a primary bronchogenic carcinoma.