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.

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.

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.

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.

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.

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.

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.

Problems related to TNM staging: patients with stage III non-small cell lung cancer.

OBJECTIVE: Many reports have raised certain problems concerning the current TNM classification of lung cancer, namely that there is no sufficient difference in prognosis between patients with pathologic stage IIIA and IIIB disease. For clarifying this problem, the present study was constructed in light of T3 and T4 classifications. METHODS: Among 429 patients with non-small cell lung cancer who underwent resection, those with stage IIIA (n = 73) and stage IIIB (n = 79) disease were enrolled in this study, and their prognostic factors were compared. RESULTS: No difference in the survivals between patients with T3 and T4 disease was observed, and this seemed to affect the prognoses of patients with stage IIIA and IIIB disease. However, when those with T3 and T4 disease were classified into different groups on the basis of TNM descriptors, differences in the survivals became evident. The T3 bronchial invasion group showed a better prognosis than the T3 extrapulmonary invasion group. The T4 tracheal invasion group and T4 pulmonary metastasis group showed a significantly better prognosis than that in the T4 extrapulmonary invasion group and the T4 malignant pleural exudate group. The surgical curativity of patients with T3 disease was evaluated as curative resection or noncurative resection, and the surgical curativity of T4 was evaluated as R0 resection or R1 or R2 resection. The T3 bronchial invasion group included more curative resection cases. The T4 tracheal invasion group and T4 pulmonary metastasis group included more R0 resection cases. Furthermore, when patients with T3 to T2 bronchial invasion and patients with T4 tracheal invasion and T4 pulmonary metastasis were reclassified as having T3 disease, the survivals of the patients reclassified as having T3 and T4 disease, as well as the resultant subsets having stage IIIA and IIIB disease, were significantly different. CONCLUSION: Tumor status should be reviewed by taking into account the surgical curativity.

Development of a canine model of pulmonary emphysema and imaging of the emphysematous lung with infrared thoracoscopy.

BACKGROUND: The surgeon must use the results of preoperative computed tomography findings and scintigraphic studies to make a subjective decision during lung volume reduction surgery with regard to the best incision line. OBJECTIVES: Our purpose was to develop an objective and real-time method of detecting areas of pulmonary emphysema by using infrared thoracoscopy. METHODS: Pulmonary emphysema was developed in various lobes of the lung in the dog by injecting porcine pancreatic elastase through the bronchi. One month after the injection, chest computed tomography and lung biopsy were performed. Infrared thoracoscopic study was then performed to reveal the presence of the emphysematous lung tissue. Simultaneously, indocyanine green was injected intravenously, and the time taken for each type of lung tissue to stain blue was measured. RESULTS: Chest computed tomography and histologic examinations revealed pulmonary emphysema-like areas in the porcine pancreatic elastase-injected lung. The computed tomography numbers of the porcine pancreatic elastase-injected lung tissue, normal lung tissue, and the tracheal lumen were -868.8 +/- 18.6, -752.2 +/- 32.5, and -1013 +/- 27.1, respectively. There were significant differences between the porcine pancreatic elastase-injected lung and the normal lung (P <.0001). The time for staining to begin was 10.7 +/- 4.8 seconds for normal lung tissue and 25.8 +/- 9.4 seconds for the emphysematous tissue; the onset of staining emphysematous lung tissue was significantly delayed (P =.003). CONCLUSIONS: We developed a successful canine model of pulmonary emphysema by injecting porcine pancreatic elastase. Infrared thoracoscopic examination revealed that the staining of emphysematous lung using indocyanine green injection was significantly greater than of normal lung.

Slow release of bone morphogenetic protein 2 from a gelatin sponge to promote regeneration of tracheal cartilage in a canine model.

OBJECTIVES: We investigated whether bone morphogenetic protein 2, released slowly from a gelatin sponge, could induce cartilage regeneration in a canine model of tracheomalacia and evaluated the long-term results. METHODS: A 1 x 5-cm gap was made in the anterior cervical trachea by removing 5-cm long strips of 10 sequential cartilagines. In the control group (n = 5), the gaps were left untreated. In the gelatin sponge group (n = 5), a gelatin sponge soaked in a buffer solution was implanted in each defect. In the bone morphogenetic protein group (n = 5), a gelatin sponge soaked in a buffer solution containing 12 microg bone morphogenetic protein 2 was implanted in each defect. RESULTS: Tracheomalacia was observed in the control and gelatin sponge groups but not in the bone morphogenetic protein group. No regenerated cartilage was detected in the control or gelatin sponge groups, even 6 months after surgery. In contrast, regenerated cartilage, which had developed from the host perichondrium, was observed around the stumps of the resected cartilagines in the bone morphogenetic protein group. This regenerated cartilage maintained the integrity of the internal lumen for longer than 6 months. A compressive fracture test revealed that the tracheal cartilage in the bone morphogenetic protein group was significantly more stable than that in the gelatin sponge and control groups (P =.0015 and P =.0001, respectively). CONCLUSIONS: In this canine model of tracheomalacia, cartilage regeneration was induced around the stumps of tracheal cartilagines by bone morphogenetic protein 2 released slowly from a gelatin sponge. This regenerated cartilage was not reabsorbed for longer than 6 months and was strong enough to maintain the integrity of the internal lumen of the trachea.

Pulmonary embolism after lung resection: diagnosis and treatment.

Pulmonary embolism after lung resection (PEALR) has a high mortality rate, and it is one of the most severe complications after lung resection. Early diagnosis and treatment are essential for PEALR. Here we present 3 cases of severe PEALR. In these cases, transthoracic Doppler echocardiography was useful for confirming the diagnosis of PEALR. Thrombolysis with recombinant tissue plasminogen activator (r-tPA) was used to treat the embolism, and these patients were subsequently discharged. Thus echocardiography may become a primary procedure to confirm the diagnosis of severe PEALR, and thrombolysis with second-generation r-tPA may be the preferred choice for treatment.

Induction chemotherapy before operation for multiple endobronchial squamous cell carcinoma of the lung.

BACKGROUND: Multiple endobronchial squamous cell carcinoma is sometimes difficult to resect due to poor pulmonary function. Although various therapeutic modalities are available, there is no consensus on the effectiveness of chemotherapy in such rare cases. In this study, we evaluated the efficacy of preoperative induction chemotherapy for patients with otherwise unresectable multiple endobronchial squamous cell carcinoma and poor pulmonary function. METHODS: Six patients with multiple endobronchial squamous cell carcinoma were enrolled in the study. They had a total of 15 foci that were in clinical stage I or II. Due to severe emphysema and poor pulmonary function, all 6 patients were considered unsuitable for complete surgical excision if either bilateral thoracotomy or pneumonectomy was required. The patients received two courses (at 3- to 4-week intervals) of induction chemotherapy, beginning on day 1 with cisplatin (80 mg/m2), vindesine (3 mg/m2), and mitomycin-C (8 mg/m2). After induction chemotherapy, surgical resection was performed on all 6 patients as bilateral thoracotomy and pneumonectomy were avoided due to the effectiveness of induction chemotherapy. RESULTS: Postoperative pathologic examination revealed a complete response in eight foci. Four nonresected foci have not recurred so far. Although three residual tumors were observed in resected specimens, they all showed moderate responses to chemotherapy. The possible complete response rate is 80%. All patients have survived for 2 to 10 years without apparent recurrence. CONCLUSIONS: Induction chemotherapy can be added to treatment options for patients with rare multiple endobronchial squamous carcinoma that cannot be resected because of poor pulmonary function.

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.

Experimental study of bone morphogenetic proteins-2 slow release from an artificial trachea made of biodegradable materials: evaluation of stenting time.

We manufactured an artificial trachea that slowly releases bone morphogenetic protein 2 (BMP-2) and used it to replace a section of the canine trachea. We made a three-layered prosthesis composed of an outer layer of gelatin sponge, a middle layer of collagen sponge, and an inner silicone tube. BMP-2 solution was soaked into the gelatin sponge layer. An approximately 3 cm length of the canine trachea was resected, and the artificial trachea was inserted into the resulting gap and anastomosed. The implanted portion was covered by periosteum. At 2, 4, and 8 weeks after surgery, the inner silicone tube was removed. Soon after removal of the silicone tube at 2 and 4 weeks, the dogs died of choking because of collapse of the trachea. One dog whose silicone tube was removed at 8 weeks was able to survive without choking. At 6 months after removal of the silicone tube, the bronchoscopic findings revealed that the gap in the trachea had been closed by regenerated tissue and covered by mucosa. We have demonstrated that our artificial trachea slowly releasing BMP-2 requires at least 8 weeks to achieve regeneration of solid tissue to support the tracheal gap.

Cartilage regeneration using slow release of bone morphogenetic protein-2 from a gelatin sponge to treat experimental canine tracheomalacia: a preliminary report.

We investigated whether saber sheath-type tracheomalacia could be treated by the slow release of bone morphogenetic protein (BMP)-2 from a gelatin sponge. A 1 cm gap was made in the middle portion of each of 10 consecutive tracheal cartilage rings in the canine cervix (control group, n = 3), then a gelatin sponge containing 12 microg of BMP-2 solution was implanted in the gap (12 microg group, n = 3). In another group (120 microg + P group, n = 3), the implanted gelatin sponge contained 120 microg of BMP-2 solution, and the gap was covered with periosteum. All of the control dogs developed saber sheath-type tracheomalacia, whereas tracheomalacia was not observed in the 12 microg and 120 microg + P groups. In the 12 microg group, fibrous cartilage was observed at the ends of the cartilage stumps. In the 120 microg + P group, newly formed bone and cartilage were observed to form a bridge between the cartilage stumps. The regeneration of cartilage or bone induced by the slow release of BMP-2 from a gelatin sponge might be useful for treatment of tracheomalacia.

Video-assisted thoracoscopic pericardial fenestration for tuberculous pericardial effusion.

A 72-year-old woman was admitted with chest discomfort and general fatigue. She was diagnosed as having cardiac tamponade with massive pericardial effusion. Percutaneous pericardiocentesis yielded bloody effusion. Tuberculous pericarditis was suspected owing to the adenosine deaminase level in this fluid. Video-assisted thoracoscopic pericardial fenestration (VATSPF) was performed for the diagnosis and treatment. Polymerase chain reaction detected Mycobacterium tuberculosis DNA in the pericardial tissues, confirming the diagnosis of tuberculous pericarditis. She received a combination of three-kind medication and anti-tuberculous regimen, and a follow-up check up for more than 2 years, exhibiting a good postoperative course. We conclude that VATSPF can be a useful procedure not only for diagnosis but for release of tuberculous pericarditis with cardiac tamponade and for prophylaxis of constrictive pericarditis.

Clinical analysis of interstitial pneumonia after surgery for lung cancer.

OBJECTIVE: The postoperative development or exacerbation of interstitial pneumonia (IP) in lung cancer patients often affects prognoses. We analyzed the patients who suffered from IP after surgery, to determine treatment and prevention of IP. METHODS: One hundred and one consecutive patients who underwent resection were enrolled in the study. Clinical background and post-, perioperative course were compared between patients who developed IP and those who did not. RESULTS: If IP developed or was exacerbated, steroid pulse (SP) therapy, immunosuppressant (IS) therapy or nitric oxide (NO) inhalation therapy was employed. Of 101 patients, 20 had suffered from IP before surgery. In four of these 20 (20%), postoperative exacerbation was observed. SP therapy was given to all patients. To one patient, IS and NO therapy were added. Three of the four patients died. 81 patients did not have IP; three of them (3.7%) developed IP after the operation and were treated with SP therapy. To one patient, IS and NO therapy were added. Two of the three patients died. IP development or exacerbation after surgery was observed in seven of 101 patients, and five of them died. It was significantly more frequent in patients with poorly differentiated squamous cell carcinoma, restrictive change in pulmonary function tests, and a low percentage diffusion capacity for carbon monoxide. Postoperative development or exacerbation was observed in patients who had undergone lobectomy or pneumonectomy. CONCLUSIONS: Postoperative IP is a serious complication. Further studies are needed to determine definitive therapeutic options. For the patients with the aforementioned risk factors, limited surgery must be considered.

[Development of new therapeutic method for empyema].

OBJECTIVES: We have investigated whether polylactic acid (PLA) sponge and fibroblast-growth-factor (FGF) released slowly from gelatin beads can induce fibrotic tissue in postpneumonectomy dead space. METHODS: Left pneumonectomy was performed in white Japanese rabbits. In the control group (N = 5), left chest was closed without any treatment. In the PLA sponge group (N = 5), PLA sponge and FGF (100 micrograms) released from gelatin beads were introduced into the left chest cavity. RESULTS: In the control group, herniation of the heart and right lung were observed without fibrotic material in the left chest cavity. In the PLA sponge group, dense fibrotic material was observed by chest CT scan 1 month after the operation. Pathological examinations revealed that PLA sponge and FGF did promote the organization of the fibrotic materials. CONCLUSIONS: Fibrotic materials can be induced in the postpneumonectomy dead space by PLA sponge and FGF released slowly from a gelatin sponge. New therapeutic method may be introduced near future by this concept, reduction of dead space with newly developed own fibrotic materials.

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).