[Bronchial carcinoid discovered due to repeated pneumonia in the lingular division of the left lung; report of a case].

Bronchial carcinoids are relatively rare, low-grade malignancies. Here we report a case of a bronchial carcinoid found by repeated pneumonia in the lingular division of the left lung. A 34-year-old man was referred to our hospital because of an abnormal shadow detected in an annual checkup. A chest computed tomography (CT) showed an infiltrative shadow in the lingular division. Two months later, a follow-up CT showed the shadow had remarkably improved. Two years after the 1st detection, an annual checkup revealed an abnormal shadow in the same lesion again. A chest CT showed not only an infiltrative shadow in the lingular division, but also a solid mass with calcification in the lingular bronchus. A bronchoscopy revealed an obstruction of the left upper lobe bronchus by a vascularized polypoid tumor. A transbronchial biopsy indicated a presence of a carcinoid, and a resection of the left upper lobe was performed. A histopathological examination showed that it was a typical carcinoid. The patient has been free of recurrence for 2 years since surgery. This is a case with repeated pneumonia and atelectasis caused by a bronchial carcinoid.

Amelioration of airway stenosis in rabbit models by photodynamic therapy with talaporfin sodium (NPe6).

It is difficult to treat patients with acquired airway stenosis, and the quality of life of such patients is therefore lowered. We have suggested the application of photodynamic therapy (PDT) as a new treatment for airway stenosis and have determined the efficacy of PDT in animal disease models using a second-generation photosensitizer with reduced photosensitivity. An airway stenosis rabbit model induced by scraping of the tracheal mucosa was administered NPe6 (5 mg kg(-1)), and the stenotic lesion was irradiated with 670 nm light emitted from a cylindrical diffuser tip at 60 J cm(-2) under bronchoscopic monitoring. PDT using NPe6 improved airway stenosis (P = 0.043) and respiratory stridor. A significant prolongation of survival time was seen in the PDT-treated animals compared to that in the untreated animals (P = 0.025) and 44% of the treated animals achieved long-term survival (>60 days). In conclusion, PDT using NPe6 is effective for improvement in airway stenosis.

Enhanced photodynamic cancer treatment by supramolecular nanocarriers charged with dendrimer phthalocyanine.

Photodynamic therapy (PDT) is a promising method for the localized treatment of solid tumors. In order to enhance the efficacy of PDT, we have recently developed a novel class of photosensitizer formulation, i.e., the dendrimer phthalocyanine (DPc)-encapsulated polymeric micelle (DPc/m). The DPc/m induced efficient and unprecedentedly rapid cell death accompanied by characteristic morphological changes such as blebbing of cell membranes, when the cells were photoirradiated using a low power halogen lamp or a high power diode laser. The fluorescent microscopic observation using organelle-specific dyes demonstrated that DPc/m might accumulate in the endo-/lysosomes; however, upon photoirradiation, DPc/m might be promptly released into the cytoplasm and photodamage the mitochondria, which may account for the enhanced photocytotoxicity of DPc/m. This study also demonstrated that DPc/m showed significantly higher in vivo PDT efficacy than clinically used Photofrin (polyhematoporphyrin esters, PHE) in mice bearing human lung adenocarcinoma A549 cells. Furthermore, the DPc/m-treated mice did not show skin phototoxiciy, which was apparently observed for the PHE-treated mice, under the tested conditions. These results strongly suggest the usefulness of DPc/m in clinical PDT.

Photodynamic therapy for airway stenosis in rabbit models.

BACKGROUND: Acquired airway stenosis in childhood is resistant to conventional treatment. We examined whether endoscope-assisted photodynamic therapy (PDT) is effective for airway stenosis in animal models of which the pathophysiologic progressions are similar to those of clinical cases showing rapid deterioration. METHODS: Tracheal mucosa-scraped rabbits were administered IV porfimer sodium (Photofrin; Wyeth K.K., Tokyo, Japan) [2 mg/kg], and the tracheal lesions were irradiated with 630 nm of light emitted from a cylindrical diffuser tip via a transtracheal approach. RESULTS: Rabbits without PDT (untreated animals) showed dense granulation tissue in the scraped lesion, resulting in airway stenosis complicated with respiratory stridor. PDT ameliorated the degree of airway stenosis (p = 0.008) and reduced respiratory stridor; rabbits that received PDT showed patchy granulation tissue that was only 20 to 30% of the volume of that seen in the untreated animals. Survival time of rabbits that received PDT was significantly prolonged compared with that of untreated animals (p = 0.03). CONCLUSIONS: PDT was effective for airway stenosis in rabbit models. This suggests that PDT has the potential as a new therapeutic method for airway stenosis originating from granulation tissue.

Accumulation of photofrin in lesions of airway stenosis rabbit models.

Airway stenosis in childhood is resistant to conventional treatments. Endoscope-assisted photodynamic therapy (PDT) is a potent candidate for the therapeutic modality owing to the easy approach to the tracheal lesion and low degree of invasiveness. The aim of the present study was to examine whether a photosensitizer preferentially accumulates in the lesion of airway stenosis in order to explore the possible applicability of PDT. The tracheal mucosa of rabbits was scraped off, and the rabbits were intravenously administered with Photofrin. The tissue concentration of Photofrin was quantitatively measured by fluorometric analysis. Granulation formation was seen in the mucosa-deprived lesion, causing airway stenosis. Photofrin concentration in the granulation tissue was four-fold higher than that in the intact trachea and 10-fold higher than that in the liver, spleen, skin and muscle. Photofrin preferentially accumulated in the lesion of airway stenosis. A preliminary experiment on PDT using transtracheal illumination showed an amelioration of airway stenosis, resulting in reduction in respiratory stridor.

Polyion complex micelles for photodynamic therapy: incorporation of dendritic photosensitizer excitable at long wavelength relevant to improved tissue-penetrating property.

A polymeric micelle (DPcZn/m) system, which is formed via an electrostatic interaction of anionic dendrimer phthalocyanine (DPcZn) and poly(ethylene glycol)-poly(l-lysine) block copolymers (PEG-b-PLL), was prepared for use as an effective photosensitizer for photodynamic therapy. DPcZn/m exhibited strong Q band absorption around 650 nm, a useful wavelength for high tissue penetration. Dynamic light scattering studies indicated that the DPcZn/m system has a relevant size of 50 nm for intravenous administration. Under light irradiation, either DPcZn or DPcZn/m exhibited efficient consumption of dissolved oxygen in a medium to generate reactive oxygen species and an irradiation-time-dependent increase in photocytotoxicity. The photodynamic efficacy of the DPcZn was drastically improved by the incorporation into the polymeric micelles, typically exhibiting more than two orders of magnitude higher photocytotoxicity compared with the free DPcZn at 60-min photoirradiation.

Significance of thymidylate synthase gene expression level in patients with adenocarcinoma of the lung.

BACKGROUND: Thymidylate synthase (TS) catalyzes the methylation of deoxyuridine monophosphate (dUMP) to deoxythymidine monophosphate (dTMP) and is a key enzyme for DNA synthesis. High expression of TS is thought to be associated with poor prognosis in some kinds of cancers. However, this association has not been clarified for nonsmall cell lung carcinoma. In the current study, the authors investigated the clinicopathologic significance of TS mRNA levels and the correlation with cellular proliferation in patients with lung adenocarcinoma. METHODS: The expression levels of TS mRNA were measured in 47 lung adenocarcinoma tissues using the Taq-Man real-time reverse transcriptase-polymerase chain reaction (RT-PCR) method and examined the clinicopathologic significance of TS expression. To clarify the correlation between TS expression level and cell proliferation, the Ki-67 labeling index was also examined using immunohistochemical staining. RESULTS: A positive correlation was observed between the expression levels of TS mRNA and stage of disease, lymph node metastasis, or tumor differentiation (P = .015). The higher expression group of TS mRNA showed a significantly poorer prognosis than the group with lower expression (P = .042). Moreover, there was a strong correlation noted between the expression levels of TS mRNA and the Ki-67 labeling index (P = .009). CONCLUSIONS: The results of the current study demonstrated that TS may be associated with stage of disease, lymph node metastasis, tumor differentiation, prognosis, and tumor cell proliferation. These results suggest that the expression levels of TS mRNA may be useful for predicting the malignant potential in patients with lung adenocarcinoma.

Rabbit model of airway stenosis induced by scraping of the tracheal mucosa.

BACKGROUND: Prolonged endotracheal intubation in children often induces intractable airway stenosis. The aim of the present study was to establish a new model of airway stenosis for developing an effective method of treatment. MATERIAL AND METHODS: The rabbit trachea was annularly incised, and the tracheal mucosa was scraped with a nylon brush. The trachea was then closed. Nine days after scraping, the trachea was microscopically examined. RESULTS: All of the examined rabbits showed tracheal stenosis, ranging from 22% to 82% in diameter and from 48% to 97% in cross-sectional area. The stenotic lesion was confined within the scraped region, not including the sutured region. Histologic examination showed inflammation in the stenotic lesion with submucosal hyperplasia caused by proliferation of fibroblasts and thickening of collagen fibers. CONCLUSION: This method can be easily carried out and assures induction of airway stenosis. This model may be useful for developing methods for treating airway stenosis in the early stage.