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1.  Clinical initiatives linking Japanese and Swedish healthcare resources on cancer studies utilizing Biobank Repositories 
The Tokyo Medical University Hospital in Japan and the Lund University hospital in Sweden have recently initiated a research program with the objective to impact on patient treatment by clinical disease stage characterization (phenotyping), utilizing proteomics sequencing platforms. By sharing clinical experiences, patient treatment principles, and biobank strategies, our respective clinical teams in Japan and Sweden will aid in the development of predictive and drug related protein biomarkers.
Data from joint lung cancer studies are presented where protein expression from Neuro- Endocrine lung cancer (LCNEC) phenotype patients can be separated from Small cell- (SCLC) and Large Cell lung cancer (LCC) patients by deep sequencing and spectral counting analysis. LCNEC, a subtype of large cell carcinoma (LCC), is characterized by neuroendocrine differentiation that small cell lung carcinoma (SCLC) shares. Pre-therapeutic histological distinction between LCNEC and SCLC has so far been problematic, leading to adverse clinical outcome. An establishment of protein targets characteristic of LCNEC is quite helpful for decision of optimal therapeutic strategy by diagnosing individual patients. Proteoform annotation and clinical biobanking is part of the HUPO initiative (http://www.hupo.org) within chromosome 10 and chromosome 19 consortia.
doi:10.1186/s40169-014-0038-x
PMCID: PMC4303744  PMID: 25635206
Cancer diseases; Protein quantification; Proteomics; Mass spectrometry; MRM; Biobanking; HUPO
2.  Cancer Phenotype Diagnosis and Drug Efficacy within Japanese Health Care 
An overview on targeted personalized medicine is given describing the developments in Japan of lung cancer patients. These new targeted therapies with novel personalized medicine drugs require new implementations, in order to follow and monitor drug efficacy and outcome. Examples from IRESSA (Gefitinib) and TARCEVA (Erlotinib) treatments used in medication of lung cancer patients are presented. Lung cancer is one of the most common causes of cancer mortality in the world. The importance of both the quantification of disease progression, where diagnostic-related biomarkers are being implemented, in addition to the actual measurement of disease-specific mechanisms relating to pathway signalling activation of disease-progressive protein targets is summarised. An outline is also presented, describing changes and adaptations in Japan, meeting the rising costs and challenges. Today, urgent implementation of programs to address these needs has led to a rebuilding of the entire approach of medical evaluation and clinical care.
doi:10.1155/2012/921901
PMCID: PMC3364583  PMID: 22685658
3.  Preferential expression of potential markers for cancer stem cells in large cell neuroendocrine carcinoma of the lung. An FFPE proteomic study 
Background
Large cell neuroendocrine carcinoma (LCNEC) of the lung, a subtype of large cell carcinoma (LCC), is characterized by neuroendocrine differentiation that small cell lung carcinoma (SCLC) shares. Pre-therapeutic histological distinction between LCNEC and SCLC has so far been problematic, leading to adverse clinical outcome. We started a project establishing protein targets characteristic of LCNEC with a proteomic method using formalin fixed paraffin-embedded (FFPE) tissues, which will help make diagnosis convincing.
Methods
Cancer cells were collected by laser microdissection from cancer foci in FFPE tissues of LCNEC (n = 4), SCLC (n = 5), and LCC (n = 5) with definite histological diagnosis. Proteins were extracted from the harvested sections, trypsin-digested, and subjected to HPLC/mass spectrometry. Proteins identified by database search were semi-quantified by spectral counting and statistically sorted by pair-wise G-statistics. The results were immunohistochemically verified using a total of 10 cases for each group to confirm proteomic results.
Results
A total of 1981 proteins identified from the three cancer groups were subjected to pair-wise G-test under p < 0.05 and specificity of a protein's expression to LCNEC was checked using a 3D plot with the coordinates comprising G-statistic values for every two group comparisons. We identified four protein candidates preferentially expressed in LCNEC compared with SCLC with convincingly low p-values: aldehyde dehydrogenase 1 family member A1 (AL1A1) (p = 6.1 × 10-4), aldo-keto reductase family 1 members C1 (AK1C1) (p = 9.6x10-10) and C3 (AK1C3) (p = 3.9x10-10) and CD44 antigen (p = 0.021). These p-values were confirmed by non-parametric exact inference tests. Interestingly, all these candidates would belong to cancer stem cell markers. Immunohistochmistry supported proteomic results.
Conclusions
These results suggest that candidate biomarkers of LCNEC were related to cancer stem cells and this proteomic approach via FFPE samples was effective to detect them.
doi:10.1186/2043-9113-1-23
PMCID: PMC3178477  PMID: 21888658
large cell neuroendocrine carcinoma; formalin-fixed paraffin embedded tissues; mass spectrometry; cancer stem cell markers
4.  Proteomic Biomarkers for Acute Interstitial Lung Disease in Gefitinib-Treated Japanese Lung Cancer Patients 
PLoS ONE  2011;6(7):e22062.
Interstitial lung disease (ILD) events have been reported in Japanese non-small-cell lung cancer (NSCLC) patients receiving EGFR tyrosine kinase inhibitors. We investigated proteomic biomarkers for mechanistic insights and improved prediction of ILD. Blood plasma was collected from 43 gefitinib-treated NSCLC patients developing acute ILD (confirmed by blinded diagnostic review) and 123 randomly selected controls in a nested case-control study within a pharmacoepidemiological cohort study in Japan. We generated ∼7 million tandem mass spectrometry (MS/MS) measurements with extensive quality control and validation, producing one of the largest proteomic lung cancer datasets to date, incorporating rigorous study design, phenotype definition, and evaluation of sample processing. After alignment, scaling, and measurement batch adjustment, we identified 41 peptide peaks representing 29 proteins best predicting ILD. Multivariate peptide, protein, and pathway modeling achieved ILD prediction comparable to previously identified clinical variables; combining the two provided some improvement. The acute phase response pathway was strongly represented (17 of 29 proteins, p = 1.0×10−25), suggesting a key role with potential utility as a marker for increased risk of acute ILD events. Validation by Western blotting showed correlation for identified proteins, confirming that robust results can be generated from an MS/MS platform implementing strict quality control.
doi:10.1371/journal.pone.0022062
PMCID: PMC3140475  PMID: 21799770
5.  Induction of E-cadherin in Lung Cancer and Interaction with Growth Suppression by Histone Deacetylase Inhibition 
We previously reported that the loss of E-cadherin confers a poor prognosis in lung cancer patients and is associated with in vitro resistance to EGFR inhibitors. We also demonstrated that ZEB-1 is the predominant transcriptional suppressor of E-cadherin in NSCLC cell lines. We now report that treatment with MS-275, compared to vorinostat (SAHA), valproic acid or TSA, was most effective in E-cadherin up-regulation and persistence in NSCLCs. As with other tumor types and HDAC inhibitors, MS-275 inhibited growth and induced apoptosis. Importantly, blocking E-cadherin induction by shRNA resulted in less inhibition by MS-275, implicating the EMT process as a contributing factor. In contrast to H460 and H661, H157 cells were resistant to E-cadherin up-regulation by HDAC inhibitors. This resistance was overcome, in a synergistic manner, by combined knockdown of ZEB-1 and ZEB-2. In addition, H157 cells stably transfected with E-cadherin were markedly attenuated in their tumor forming ability. Lastly, combining MS-275 with the microtubule stabilizing agent, paclitaxel, or 17-AAG, an HSP 90 inhibitor, resulted in synergistic growth inhibition. Since MS-275 has no reported activity against HDAC6, which regulates both microtubule and HSP 90 functions, other mechanisms of synergy are anticipated. These results support the role of ZEB proteins and HDAC inhibitors in the pathogenesis and treatment of lung cancer.
doi:10.1097/JTO.0b013e3181bc9419
PMCID: PMC2796578  PMID: 20009910
lung cancer; histone deacetylase; Vorinostat; E-cadherin; ZEB; 17-AAG; paclitaxel NCI-H157; NCI-H661
6.  Polymorphisms, Mutations, and Amplification of the EGFR Gene in Non-Small Cell Lung Cancers 
PLoS Medicine  2007;4(4):e125.
Background
The epidermal growth factor receptor (EGFR) gene is the prototype member of the type I receptor tyrosine kinase (TK) family and plays a pivotal role in cell proliferation and differentiation. There are three well described polymorphisms that are associated with increased protein production in experimental systems: a polymorphic dinucleotide repeat (CA simple sequence repeat 1 [CA-SSR1]) in intron one (lower number of repeats) and two single nucleotide polymorphisms (SNPs) in the promoter region, −216 (G/T or T/T) and −191 (C/A or A/A). The objective of this study was to examine distributions of these three polymorphisms and their relationships to each other and to EGFR gene mutations and allelic imbalance (AI) in non-small cell lung cancers.
Methods and Findings
We examined the frequencies of the three polymorphisms of EGFR in 556 resected lung cancers and corresponding non-malignant lung tissues from 336 East Asians, 213 individuals of Northern European descent, and seven of other ethnicities. We also studied the EGFR gene in 93 corresponding non-malignant lung tissue samples from European-descent patients from Italy and in peripheral blood mononuclear cells from 250 normal healthy US individuals enrolled in epidemiological studies including individuals of European descent, African–Americans, and Mexican–Americans. We sequenced the four exons (18–21) of the TK domain known to harbor activating mutations in tumors and examined the status of the CA-SSR1 alleles (presence of heterozygosity, repeat number of the alleles, and relative amplification of one allele) and allele-specific amplification of mutant tumors as determined by a standardized semiautomated method of microsatellite analysis. Variant forms of SNP −216 (G/T or T/T) and SNP −191 (C/A or A/A) (associated with higher protein production in experimental systems) were less frequent in East Asians than in individuals of other ethnicities (p < 0.001). Both alleles of CA-SSR1 were significantly longer in East Asians than in individuals of other ethnicities (p < 0.001). Expression studies using bronchial epithelial cultures demonstrated a trend towards increased mRNA expression in cultures having the variant SNP −216 G/T or T/T genotypes. Monoallelic amplification of the CA-SSR1 locus was present in 30.6% of the informative cases and occurred more often in individuals of East Asian ethnicity. AI was present in 44.4% (95% confidence interval: 34.1%–54.7%) of mutant tumors compared with 25.9% (20.6%–31.2%) of wild-type tumors (p = 0.002). The shorter allele in tumors with AI in East Asian individuals was selectively amplified (shorter allele dominant) more often in mutant tumors (75.0%, 61.6%–88.4%) than in wild-type tumors (43.5%, 31.8%–55.2%, p = 0.003). In addition, there was a strong positive association between AI ratios of CA-SSR1 alleles and AI of mutant alleles.
Conclusions
The three polymorphisms associated with increased EGFR protein production (shorter CA-SSR1 length and variant forms of SNPs −216 and −191) were found to be rare in East Asians as compared to other ethnicities, suggesting that the cells of East Asians may make relatively less intrinsic EGFR protein. Interestingly, especially in tumors from patients of East Asian ethnicity, EGFR mutations were found to favor the shorter allele of CA-SSR1, and selective amplification of the shorter allele of CA-SSR1 occurred frequently in tumors harboring a mutation. These distinct molecular events targeting the same allele would both be predicted to result in greater EGFR protein production and/or activity. Our findings may help explain to some of the ethnic differences observed in mutational frequencies and responses to TK inhibitors.
Masaharu Nomura and colleagues examine the distribution ofEGFR polymorphisms in different populations and find differences that might explain different responses to tyrosine kinase inhibitors in lung cancer patients.
Editors' Summary
Background.
Most cases of lung cancer—the leading cause of cancer deaths worldwide—are “non-small cell lung cancer” (NSCLC), which has a very low cure rate. Recently, however, “targeted” therapies have brought new hope to patients with NSCLC. Like all cancers, NSCLC occurs when cells begin to divide uncontrollably because of changes (mutations) in their genetic material. Chemotherapy drugs treat cancer by killing these rapidly dividing cells, but, because some normal tissues are sensitive to these agents, it is hard to kill the cancer completely without causing serious side effects. Targeted therapies specifically attack the changes in cancer cells that allow them to divide uncontrollably, so it might be possible to kill the cancer cells selectively without damaging normal tissues. Epidermal growth factor receptor (EGRF) was one of the first molecules for which a targeted therapy was developed. In normal cells, messenger proteins bind to EGFR and activate its “tyrosine kinase,” an enzyme that sticks phosphate groups on tyrosine (an amino acid) in other proteins. These proteins then tell the cell to divide. Alterations to this signaling system drive the uncontrolled growth of some cancers, including NSCLC.
Why Was This Study Done?
Molecules that inhibit the tyrosine kinase activity of EGFR (for example, gefitinib) dramatically shrink some NSCLCs, particularly those in East Asian patients. Tumors shrunk by tyrosine kinase inhibitors (TKIs) often (but not always) have mutations in EGFR's tyrosine kinase. However, not all tumors with these mutations respond to TKIs, and other genetic changes—for example, amplification (multiple copies) of the EGFR gene—also affect tumor responses to TKIs. It would be useful to know which genetic changes predict these responses when planning treatments for NSCLC and to understand why the frequency of these changes varies between ethnic groups. In this study, the researchers have examined three polymorphisms—differences in DNA sequences that occur between individuals—in the EGFR gene in people with and without NSCLC. In addition, they have looked for associations between these polymorphisms, which are present in every cell of the body, and the EGFR gene mutations and allelic imbalances (genes occur in pairs but amplification or loss of one copy, or allele, often causes allelic imbalance in tumors) that occur in NSCLCs.
What Did the Researchers Do and Find?
The researchers measured how often three EGFR polymorphisms (the length of a repeat sequence called CA-SSR1, and two single nucleotide variations [SNPs])—all of which probably affect how much protein is made from the EGFR gene—occurred in normal tissue and NSCLC tissue from East Asians and individuals of European descent. They also looked for mutations in the EGFR tyrosine kinase and allelic imbalance in the tumors, and then determined which genetic variations and alterations tended to occur together in people with the same ethnicity. Among many associations, the researchers found that shorter alleles of CA-SSR1 and the minor forms of the two SNPs occurred less often in East Asians than in individuals of European descent. They also confirmed that EGFR kinase mutations were more common in NSCLCs in East Asians than in European-descent individuals. Furthermore, mutations occurred more often in tumors with allelic imbalance, and in tumors where there was allelic imbalance and an EGFR mutation, the mutant allele was amplified more often than the wild-type allele.
What Do These Findings Mean?
The researchers use these associations between gene variants and tumor-associated alterations to propose a model to explain the ethnic differences in mutational frequencies and responses to TKIs seen in NSCLC. They suggest that because of the polymorphisms in the EGFR gene commonly seen in East Asians, people from this ethnic group make less EGFR protein than people from other ethnic groups. This would explain why, if a threshold level of EGFR is needed to drive cells towards malignancy, East Asians have a high frequency of amplified EGFR tyrosine kinase mutations in their tumors—mutation followed by amplification would be needed to activate EGFR signaling. This model, though speculative, helps to explain some clinical findings, such as the frequency of EGFR mutations and of TKI sensitivity in NSCLCs in East Asians. Further studies of this type in different ethnic groups and in different tumors, as well as with other genes for which targeted therapies are available, should help oncologists provide personalized cancer therapies for their patients.
Additional Information.
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0040125.
US National Cancer Institute information on lung cancer and on cancer treatment for patients and professionals
MedlinePlus encyclopedia entries on NSCLC
Cancer Research UK information for patients about all aspects of lung cancer, including treatment with TKIs
Wikipedia pages on lung cancer, EGFR, and gefitinib (note that Wikipedia is a free online encyclopedia that anyone can edit)
doi:10.1371/journal.pmed.0040125
PMCID: PMC1876407  PMID: 17455987
7.  An Early Stage Diffuse B-Cell Lymphoma Within a Visible Site of Bronchofiberscope Accompanied by Peripheral Lung Cancer 
We report a case of non-Hodgkin's lymphoma found at the orifice of right B2 accompanied by peripheral lung cancer in a 66-year-old asymptomatic man. Chest X-ray films showed a mass shadow in the left lower lung field. Transbronchial lung biopsy of left S9 demonstrated squamous cell carcinoma. Simultaneously wall thickening at the orifice of the right B2 was found coincidentally. The biopsy specimen from that site showed non-Hodgkin's lymphoma (diffuse B-cell type). After left lower lobectomy, systemic chemotherapy was performed. It is rare for malignant lymphoma to be recognized bronchofiberscopically.
doi:10.1155/DTE.6.179
PMCID: PMC2362766  PMID: 18493536
8.  Analysis of the Cost-effectiveness of Photodynamic Therapy in Early Stage Lung Cancer 
Methods A cost-effectiveness analysis was carried out for photodynamic therapy (PDT) performed in early stage lung cancer cases, which by definition have no lymph node metastasis. The alternative treatment method was lobectomy, which conventionally would have been the first choice of treatment. Costs (C) and effectiveness (E) both of the PDT group and operation group were compared. Effectiveness was determined using quality adjusted life years saved (QALYs) which is the 5-year survival rate adjusted in terms of the quality of life of the patient, and the cost-effectiveness rate was obtained based on the costs of treatment methods during the patient's stay in the hospital. Health care costs, including drugs, were calculated according to the 1992 National Health Insurance list in yen. Costs which were non-reimbursable by the public insurance system, such as for special rooms and sun block cream, were also expressed in yen.
Results The total cost of the operated group was ¥1,793,832 and that for the PDT group was ¥1,017,104. The cost-effectiveness rate of the operated group, that is the average cost of treatment per postoperative living month, was ¥37,537, while that of the entire PDT group was ¥30,003. This indicates that the cost-effectiveness rate for the operated group is apparently 1.3 times higher than that of the PDT group. The monthly cost-effectiveness rate for the PDT group of lesions smaller than 2 cm was ¥25,533. Therefore the cost in the operated group is 1.5 times higher.
Conclusions This study demonstrated the merits of PDT for early stage lung cancer from the point of view of cost-effectiveness.
doi:10.1155/DTE.6.9
PMCID: PMC2362751  PMID: 18493519
9.  The Development of a New Setup for Video-assisted Thoracic Surgery 
In order to accomplish video-assisted thoracic surgery (VATS) in a much easier and safer way, especially for assistant operators, we have developed a new display system for VATS. The original thoracoscope has been designed for this new system. The monitor is fixed at approximately 10 cm away from the surface of the chest wall just above the operative field. In using this procedure, the operator and assistants can see the patient and the monitor at the same time. According to this new idea, the previous problem in the area of hand–eye coordination and the three-dimensional understanding of this procedure can be improved compared to the image of the conventional thoracoscopy, because it is not necessary for the operator and assistants to look up at the monitors. When the thoracoscopy was placed in an adequate position to resect the target pathology, this new system led to good and easy handling of instruments, as it was with the standard thoracotomy.
doi:10.1155/DTE.6.43
PMCID: PMC2362750  PMID: 18493525
10.  A Case of Endobronchial Lipoma 
Endobronchial lipomas are very rare tumors originating from the tracheo-bronchial wall. We have experienced a case of endobronchial lipoma which was found at the orifice of the left lower lobe bronchus and obstructive pneumonia distal to it. Left lower lobectomy was performed, and the patient has been well without any symptoms so far.
Endobronchial lipomas are histologically benign tumors, but more than half of the reported cases underwent lobectomy or pneumonectomy due to the presence of varying degrees of irreversible peripheral lung damages.
doi:10.1155/DTE.5.263
PMCID: PMC2362642  PMID: 18493511
11.  Effectiveness of Photodynamic Therapy and Nd-YAG Laser Treatment for Obstructed Tracheobronchial Malignancies 
Since 1980, advanced lung carcinomas were treated with palliative laser therapy for the purpose of opening the endobronchial stenosis and obstruction by either photodynamic therapy (PDT) or Nd-YAG laser treatment at Tokyo Medical University. A total of 258 lesions were treated, 81 by PDT and 177 by Nd-YAG laser treatment. PDT achieved effective results in 61 (75%) of 81 lesions. In the Nd-YAG laser group, 143 (81%) of 177 lesions showed effective results. When the tumor was located in the trachea or main bronchi, effective results were obtained in 73% (19 of 26) of cases treated by PDT and in 93% of cases (64 of 69) treated by Nd-YAG laser. However, in cases in which the tumor was located in lobar or segmental bronchi, the tumor response was effective in 76% (42 of 55) of PDT-treated patients and 73% (79 of 108) of Nd-YAG laser-treated patients. With a mortality rate of 0%, the greatest advantage of PDT over Nd-YAG treatment was safety. Considering complications, PDT seems to be useful for obstruction of lobar and segmental bronchus. Nevertheless, when deciding among alternative therapies, physicians treating patients with advanced lung carcinoma should give careful consideration to the benefit and complications of both laser therapies and decide the most suitable modality.
doi:10.1155/DTE.5.161
PMCID: PMC2362634  PMID: 18493498
12.  Lung Cancers Treated With Photodynamic Therapy and Surgery 
Laser endoscopic surgery, especially the effectiveness of photodynamic therapy (PDT) using Photofrin as a photosensitizer, has now achieved a status as effective treatment modality for lung cancer. Twenty-six lung cancer patients received the preoperative PDT for the purpose of either reducing the extent of resection or increasing operability. Bronchoscopical PDT is performed with topical anesthesia approximately 48 h after the intravenous injection of 2.0 mg/kg body weight of Photofrin. Operation was performed 2–9 weeks after initial PDT. The initial purpose of PDT, i.e. either to reduce the extent of resection or convert inoperable disease to operable status, was achieved in 22 out of 26 patients treated. The survival rate of T3 (main bronchus invasion) cases treated by surgery alone increased significantly from 50.9% to 60.0% with the application of preoperative PDT. This remarkable result may imply that this new option of PDT as preoperative laser irradiation may contribute to the management of advanced lung malignancy.
doi:10.1155/DTE.5.155
PMCID: PMC2362632  PMID: 18493497
13.  Preface 
doi:10.1155/S1070360899000168
PMCID: PMC2362630  PMID: 18493495
14.  Preface 
doi:10.1155/DTE.5.vii
PMCID: PMC2362622  PMID: 18493481
15.  Early Detection of Bronchial Lesions Using System of Autofluorescence Endoscopy (SAFE) 1000 
Recently several endoscopic fluorescence detection systems have been developed. In some of them, laser light was used for the excitation of autofluorescence, and sophisticated techniques were also necessary to amplify the fluorescence signal as well.
The result of fluorescence diagnosis using a simple system with a conventional Xenon lamp excitation and an image intensifier is reported. The respective results of sensitivity and positive predictive values of cancer plus dysplasia were 66%, and 62% by standard bronchoscopy and 92% and 88% by the newly developed autofluorescence system. In this paper, developed endoscope for detection of tissue/mucosal autofluorescence without the application of any photosensitizing agents or use of any lasers is evaluated.
doi:10.1155/DTE.5.99
PMCID: PMC2362620  PMID: 18493488
16.  Cooperative Clinical Trial of Photodynamic Therapy for Early Gastric Cancer With Photofrin Injection® and YAG-OPO Laser 
Background and Objective: Photodynamic therapy (PDT) treats malignant tumors using photosensitizers and light. We employed a new pulse laser as the excitation light source for PDT, i.e. an optical parametric oscillator (OPO) system pumped by a Q-switched Nd:YAG laser, because it provides extremely high peak power.
Study Design/Materials and Methods: The effects of PDT using the photosensitizer Photofrin® and the new laser were evaluated in 12 patients with early gastric cancer.
Results: Complete responses (CR) were obtained in 75% of 12 assessable patients, CR was observed in all cases with mucosal carcinoma (response rate 100%).
Regarding toxicity, mild photosensitivity was seen in one case and it lasted several weeks. The other major side effect was decrease of total protein, which was observed in six patients (40%), lasting several months. There were no serious abnormalities in symptoms or laboratory tests.
Conclusion: We conclude that the YAG-OPO laser is suitable as an excitation light source for PDT.
doi:10.1155/DTE.4.165
PMCID: PMC2362606  PMID: 18493468
17.  A Clinical Study of Photodynamic Therapy for Superficial Esophageal Carcinoma by YAG-OPO Laser 
A cooperative clinical study of photodynamic therapy (PDT) for superficial esophageal carcinoma was conducted at 6 medical institution. PHE (2mg/kg) with high tumor affinity was used as the oncotropic compound. The light source was a pulse wave YAG-OPO laser with high penetration into the tissue. Irradiation was performed at an energy density of 60–180 J/cm2 48–72 h after PHE administration. Eight lesions in 6 patients were treated. All were type 0-II superficial carcinomas. The depth of invasion was EP–MM for 6 lesions and SM for 2 lesions. A complete response (CR) was achieved in all patients after one session of PDT. Five adverse events, including anemia and fever, were reported by 4 patients, but all were WHO grade 2 or lower and transient. PDT using PHE and YAG-OPO laser was therefore considered effective as a curative therapy for superficial esophageal carcinoma.
doi:10.1155/DTE.4.173
PMCID: PMC2362605  PMID: 18493469
18.  Fiberoptic Bronchoscopy in Thyroid Carcinoma With Tracheal Invasion 
Preoperative bronchoscopic findings of thyroid carcinoma with tracheal invasion were examined and compared with the histopathological findings. Tracheal sleeve resection was performed in 20 cases. The bronchoscopic findings were classified into 5 types: confirmed tumor in the tracheal lumen (5 cases), extramural compression of the trachea plus mucosal change (9 cases), extramural compression of the trachea (2 cases), mucosal changes only (3 cases), normal findings (1 case). Pathological findings revealed that the extent of invasion in the tracheal wall varied according to each of the above bronchoscopic types. The number of tracheal rings with adventitial invasion averaged 0.8 (maximum 2) more than preoperative bronchoscopic findings of the number of tracheal rings with mucosal invasion. This study demonstrated the necessity of resective 2 more tracheal rings than is indicated by the bronchoscopic findings.
doi:10.1155/DTE.4.113
PMCID: PMC2362597  PMID: 18493461
19.  Photodynamic Therapy With YAG-OPO Laser for Early Stage Lung Cancer 
Photodynamic therapy (PDT) utilizing Photofrin is proving to be effective for the treatment of early stage lung cancers. The effect of PDT utilizing YAG-OPO laser as new light source was evaluated in 26 patients (29 lesions) with early stage lung cancers. YAG-OPO laser is solid state tunable laser which is easy to change wavelength between 620 and 670 nm exciting various kinds of photosensitizers. Moreover, YAG-OPO laser is more reliable, smaller and has less consumables than argon-dye laser or excimer-dye laser. As the result of PDT with YAG-OPO laser, complete remission (CR) was obtained in 82.6% of the 29 lesions, partial remission (PR) in 13.8% and no change (NC) was obtained in 3.4%. We conclude that PDT utilizing YAG-OPO laser is efficacious in the treatment of early stage lung cancers and can achieve complete remission.
doi:10.1155/DTE.4.75
PMCID: PMC2362591  PMID: 18493456
20.  Synchronous Quadruple Lung Cancer Treated Curatively by Photodynamic Therapy 
A 54-year-old male was diagnosed as having synchronous quadruple early stage lung cancer. All four tumors showed the same histologic type of in-situ or microinvasive squamous cell carcinoma, but existed independently in different bronchi. Photodynamic therapy of these four lesions was successfully performed by fiberoptic bronchoscopy because of the patient's poor pulmonary function. The patient is alive and well 51 months later.
doi:10.1155/DTE.3.115
PMCID: PMC2362555  PMID: 18493426
21.  Photodynamic Therapy for Head and Neck Cancer 
Photodynamic therapy (PDT) is a recently developed treatment involving the use of a photosensitizer and low power light, usually from a laser, to selectively destroy tumor cells. At present, we perform PDT for head and neck cancer using argon or excimer dye lasers with hematoporphyrin derivative as a photosensitizer. This study attempted to assess the utility and safety of PDT and to investigate the long-term outcome. All 24 patients had squamous cell carcinoma: 15 with laryngeal, 5 with lingual or oral, and 4 with pharyngeal cancer and were treated by PDT. Data were obtained from records from February 1988 through April 1995. After PDT, 12 of 15 laryngeal cancer patients were classified as having a complete remission (CR), as were 2 of the 5 lingual or oral and one of the 4 pharyngeal cancer patients. The patients were followed for 8 to 153 months. The longest duration of CR in patients treated by PDT alone was 148 months. Photosensitivity was experienced by all patients, but required no treatment. Liver, kidneys, and bone marrow showed no abnormal values. There were no clinically relevant adverse reactions, and patients with severe complications due to other types of treatment and elderly patients were also treated safely with this therapy.
doi:10.1155/DTE.3.41
PMCID: PMC2362549  PMID: 18493416
22.  Photodynamic Therapy of Lung Cancer With Bronchial Artery Infusion of Photofrin 
Photodynamic therapy (PDT) utilizing Photofrin is proving to be effective for the treatment of early stage lung cancer. However, wider clinical applications of Photofrin as a photosensitizer for various cancers are hampered by potentially serious and prolonged skin photosensitivity. To prevent these side effects and reduce the hospitalization period, we recently gave reduced doses of Photofrin by bronchial arterial infusion. Five patients with endoscopically evaluated minimally invasive carcinoma of the lung were given 0.7 mg/kg of Photofrin by bronchial arterial infusion 48 hr before PDT. Complete remission was obtained in all 5 cases and no case showed skin photosensitivity when exposed to sunlight under careful surveillance at one week after PDT.
doi:10.1155/DTE.2.203
PMCID: PMC2362536  PMID: 18493405
23.  A Unique Case of Adenoid Cystic Carcinoma of the Left Main Bronchus 
A unique case of adenoid cystic carcinoma of the left main bronchus is reported.
doi:10.1155/DTE.1.237
PMCID: PMC2362486  PMID: 18493373
24.  Application of Simple Imaging Technique for Fluorescence Bronchoscope 
It was reported that the significant spectral difference of autofluroescence induced by laser light between cancer and normal tissue. A fluorescence bronchoscope system with simple light source and light filter was newly developed. In this paper, the detection of autofluorescence from bronchogenic dysplasia with this system was reported.
doi:10.1155/DTE.1.79
PMCID: PMC2362469  PMID: 18493346
25.  Introduction 
doi:10.1155/DTE.1.vii
PMCID: PMC2362461  PMID: 18493333

Results 1-25 (26)