Search

The cut-and-sew Maze procedure has historically been the most efficacious therapy for patients with atrial fibrillation (AF) that is refractory to medical management, but is not widely used as a stand-alone treatment for AF. New ablation technologies can create pulmonary vein (PV) isolation without cardiopulmonary bypass.The 'thoracoscopic mini-Maze' procedure includes bilateral PV isolation, ablation of the epicardial ganglionated plexi and excision of the left atrial appendage using small bilateral thoracotomies with thoracoscopic assistance. Between January 2006 and April 2007, 20 thoracoscopic mini-Maze procedures were performed at 2 institutions and over a mean follow-up of 16.6 months, 18 (90%) patients are in sinus rhythm. Perioperative bleeding complications occurred in 3 patients (15%) and there was 1e (5%) late instance of atrial flutter that required a right-sided ablation. None of the patients died or needed a pacemaker.Early experience with the thoracoscopic mini-Maze procedure suggests that sinus rhythm can be re-established in most patients in the short-term and with more experience the rate of complications should reduce, which is required prior to defining the role of this therapy in the future treatment of AF.

Publisher Summary This chapter presents the usefulness and pitfalls of a mass screening for lung cancer with low-dose helical CT (LDHCT) scan and presents the Mayo Clinic project of lung cancer screening LDHCT scan. The helical CT scan has the highest sensitivity for the detection of pulmonary nodules compared to other examinations. LDHCT might be a promising method for screening early lung cancer at health examinations. Most of the lung cancers detected in lung cancer screening with LDHCT are stage I. Well-designed clinical trials are necessary to establish the guidelines for mass screening for lung cancer. The Mayo Clinic investigated the trial of LDHCT screening for lung cancer initiated in 1999. High-risk participants more than 50 years of age and with 20 pack-years of smoking or more were listed. Low-dose helical CT with multislice CT (MSCT, four detectors) was used under conditions that included 5 mm collimation with 3.75 mm reconstruction. At least one noncalcified nodule was detected in 780 of 1520 (51%) participants on the baseline CT scan, and a total of 3356 noncalcified nodules were detected in the 1118 participants from 2000 through 2003. Some participants with pulmonary nodules undergo thoracic surgery and/or biopsies, such as transbronchial lung biopsy (TBLB) for benign disease. The rate of invasive procedures, such as TBLB and conventional thoracotomy, for benign lesions detected by computed tomography (CT) screening was 22-55% of participants with abnormal CT findings. The General Rule for the Clinical and Pathological Record of Lung Cancer (GRCPRLC) notes that further clinical examinations are necessary for cases with nodules >10 mm in diameter in helical CT screening for lung cancer.

We report herein the case of a 30-year-old man who developed a primary leiomyosarcoma (LMS) 11 years after undergoing a median sternotomy for mediastinal seminoma followed by 50 Gy radiotherapy. He was given two courses of chemotherapy, resulting in 90% tumor regression, after which resection of the tumor with adjacent chest wall structures was carried out. Reconstruction was performed using a methylmethacrylate prosthesis prepared preoperatively. Post-operatively, he received two additional courses of chemotherapy and has had no sign of recurrence for 45 months.

One-Step Dry-Coated tablets (OSDrC) of a colon-targeting drug were prepared using Eudragit L 100-55 (Eud-L) and chitosan (Chit) as the outer layer. Lag time in the 1st fluid, which simulated the stomach, was affected by differences in the pores occurring as a result of Chit dissolution. The dissolution rate of Chit was decreased by the addition of Eud-L. On the other hand, lag times in phosphate buffer (pH 7.4) simulating the small intestine, and in the 2nd fluid simulating the colon, were affected by differences in the pores occurring as a result of Eud-L dissolution and Chit swelling. The lag time of OSDrC with an outer layer of Eud-L:Chit at a ratio of 3:1 in each test medium was greater than the gastric emptying time in the 1st fluid and the small intestine transit time in phosphate buffer (pH 7.4). Furthermore, lag times were similar when test media were changed sequentially. Therefore, it is possible to deliver colon-targeting drugs as OSDrC with an outer layer of Eud-L:Chit at 3:1.

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.

It is not well understood what kind of histologic resolution is obtained with corticosteroid medication in sarcoidosis, or how we are able to judge cure in that disease. We examined the cases of sarcoidosis who were under steroid medication and received lobectomy and lymphadenectomy for combined lung cancer. Steroid treatment had been introduced for the relief of visual disturbance, not for the pulmonary lesion. Administration of corticosteroid improves clinical, laboratory, bronchoalveolar lavage and radiological findings, but it is difficult to make histological granulomatous inflammation completely disappear. Improvement of radiological and clinical problems in sarcoidosis is not the same as complete cure in patients with steroid-treated sarcoidosis.

Amplification of chromosomal DNA is thought to be one of the mechanisms that activates cancer-related genes in tumors. In a previous genome-wide screening of DNA copy number aberrations in a panel of non-small cell lung cancer (NSCLC) cell lines using an in-house bacterial artificial chromosome-based array, we identified a novel amplification at 14q11.2 in HUT29 cells derived from human lung adenocarcinoma. To identify the most likely target for the 14q11.2 amplification, we determined the extent of the amplicon by fluorescence in situ hybridization and then analyzed NSCLC cell lines for the expression levels of 28 genes present within the 1-Mb amplified region. Significant overexpression in the HUT29 cell line with amplification, relatively frequent overexpression in additional NSCLC cell lines compared with an immortalized normal lung epithelial cell line, and reported information about the function of each candidate gene prompted us to characterize the BCL2-like2 (BCL2L2) gene, a prosurvival member of the BCL2 family, as the most likely target for the 14q11.2 amplicon. Immunohistochemical analysis of 61 primary cases of lung adenocarcinoma demonstrated that BCL2L2 overexpression was significantly associated with tumor stage and differentiation status, and tended to be associated with a poorer prognosis. Downregulation of BCL2L2 expression using small interfering RNA dramatically inhibited the growth of HUT29 cells, but showed no effect on anticancer reagent-induced cell death of the same cell line. These findings demonstrate that overexpressed BCL2L2, through amplification or other mechanisms, promotes the growth of NSCLC, especially the adenocarcinoma subtype, and might be a therapeutic target.

A 60-year-old man was given a diagnosis of pulmonary and ocular sarcoidosis. His radiological abnormalities and visual disturbance resolved after two years. Ten years later, at age 70, squamous cell carcinoma was detected in the right lower lobe of the lung. Lymphocyte CD4/8 ratio in bronchoalveolar lavage fluid has remained at a high level for the previous 10 years and was 7.41 immediately before the operation. Chest CT and gallium scintigram could not detect abnormalities in mediastinal or hilar nodes. The tumor and right lower lobe were resected with hilar and mediastinal lymph nodes. Histological examination revealed that there were numerous epithelioid cell granulomas in mediastinal and hilar lymph nodes. BALF analysis reflects residual granulomatous inflammation, even if the radiological findings do not show any abnormalities.

A novel method of manufacturing one-step dry-coated (OSDRC) tablets, which we recently invented, was used to produce sugar-coated tablets protected from moisture without the need for a conventional complicated sugar coating process. Amorphous sucrose was selected for the outer layer of the OSDRC tablets as sugar-coated layer. The isothermal crystallization behavior and characteristics such as water vapor permeability, tensile strength, and disintegration time of compressed amorphous sucrose were investigated. Water vapor adsorption measurements showed the crystallization behavior of amorphous tablets to be similar to that of amorphous powder, although it was affected by compression pressure. We found that the crystallized amorphous sucrose after compression at 200 MPa was moisture protective, and the water vapor permeability coefficient was decreased to 1/2000 or less compared with a tablet prepared with a lactose-microcrystalline cellulose (MCC) mixture, hydroxypropylmethylcellulose (HPMC), and sucrose crystal. The water vapor permeability and physicochemical characteristics were influenced by the amorphous content or additive content. It was confirmed that a new sugar-coated tablet using amorphous sucrose and OSDRC technology was moisture protective, therefore, it was concluded that the novel sugar coating method was very useful to obtain a moisture protective tablet.

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. Cancer 2006. © 2006 American Cancer Society.

A photocrosslinkable chitosan (Az-CH-LA) aqueous solution containing paclitaxel resulted in an insoluble hydrogel within 30 s of ultrtaviolet light (UV)-irradiation. About 35-40% of the paclitaxel was released from the paclitaxel-incorporated chitosan hydrogel into phosphate buffered saline (PBS) within 1 day, after which gradual release occurred during 3 days under in vitro non-degradation conditions of the hydrogel. The paclitaxel remaining in the chitosan hydrogel retained its biological activity in vitro for at least 21 days, and was released from the chitosan hydrogel in vivo upon degradation of the hydrogel. The paclitaxel-incorporated Az-CH-LA hydrogel inhibited the growth of subcutaneously induced tumors with Lewis lung cancer (3LL) cells more effectively than those treated with only Az-CH-LA, only paclitaxel, and a non-treated group (control) for at least 11 days. Furthermore, paclitaxel-incorporated chitosan hydrogel markedly reduced the number of CD34-positive vessels in subcutaneous 3LL tumors, indicating a strong inhibition of angiogenesis. These results suggested that application of paclitaxel-incorporated Az-CH-LA hydrogel has an inhibitory activity on angiogenesis and tumor growth.

To comparatively assess the interpretation performance of hard-copy versus soft-copy presentations for detecting subtle pulmonary lesions and to estimate soft-copy cost-effectiveness.Computed radiography was used to obtain images with a 1,600x 1,200 matrix having 8 bits of gray-scale definition. The two separate image formats (hard and soft copy), which consisted of 60 chest radiograph combinations, were shown to five board-certified radiologists. The costs of hard copies, chemicals, waste disposal, and labor were calculated.The mean accuracies and Az values were 0.63 (hard) vs. 0.64 (soft) and 0.657 (hard) vs. 0.729 (soft), respectively. Reading one set of hard copies took on average 8.0 sec less than reading soft copies (30.3 vs. 38.3 sec). Estimated savings resulting from replacement of hard copy with soft were US$128,004 per year or US$6.20 per patient at our hospital.Conversion from hard copy to soft copy, using image processing, is feasible and cost-effective.

A pulmonary nodule was incidentally detected in a 50-year-old man during a routine health evaluation. High-resolution computed tomography (HRCT) showed that the lesion had the appearance of a collection of multiple tiny nodules. Histologic examination of the resected specimen revealed a single hamartoma resembling a bunch of grapes. Pulmonary alveoli and bronchioles were entrapped within the hamartoma with tumor buds appearing in a multicentric manner, thereby producing the unusual HRCT findings. Review of chest radiographs taken over the previous 20 years indicated that the tumor doubling time was 4968 days.

Using a novel one-step dry-coated tablets (OSDRC) manufacturing method, which we have recently invented, we evaluated the possibility of its application to delayed-release tablets. The manufacturing method for OSDRC is different from conventional methods in that dry-coated tablets can be made with only one process. One of the major advantages of OSDRC is that we can expect to produce tablets, which always contain the core exactly in the center of the whole tablet. This characteristic means that the thickness of outer layer is constantly uniform, which is difficult to achieve with the conventional dry-coated tablets. The effects of different outer layer thicknesses and various compression pressures were examined using HPMC to evaluate OSDRC applicability to delayed-release tablets. We proved that the lag-time can be adjusted only by changing the thickness of the outer layer without any arrangement of its ingredients, which is quite different from the conventional approach. Further, the lag-time of each OSDRC prepared in the 100-200 MPa compression pressure range was almost the same, indicating the lag-time of OSDRC under these compression pressures does not vary. The release rate of the drug (acetaminophen) from the OSDRC with 0.5 and 1.0 mm outer layer thicknesses was almost constant independent of compression pressure. On the other hand, the release rate of the OSDRC with a 2.0 mm outer layer thickness was delayed compared to that of other thicknesses. That is, in the tablets with 2.0 mm outer layer thickness, the release rate declined since its outer layer thickness was sufficient to form a gel-layer. In conclusion, OSDRC could be a platform for delayed-release tablets, which do not utilize the conventional method used for dry-coated tablets.

One-step dry-coated tablets (OSDRC) were prepared using materials which are generally used in pharmaceutical tablets. The radial tensile strength of OSDRC was measured for various compression pressures and core porosities before the final compression to compare with that of conventional dry-coated tablets (DC). Furthermore, stress relaxation in the compression process was investigated. Radial tensile strength and stress relaxation profiles of OSDRC were the same as those of conventional DC. X-ray computerized tomography (CT) of the tablets showed that the density distribution of both tablets was also the same. Thus, we concluded that OSDRC and conventional DC have the same compression characteristics and physical properties. The OSDRC-system was executed by the use of upper and lower punches, which had a double structure, a center punch, and an outer punch surrounding the center punch. The OSDRC process consists of three compressions to make the lower-outer layer (1st-outer layer), the core, and the whole tablet including the upper-outer and side-outer layers (2nd-outer layer). At first, the powder for the 1st-outer layer fills a space, which is made by the lower-center punch and lower-outer punch, and is pre-compressed by the upper-center punch. Then, while the upper-center punch pushes the pre-compressed 1st-outer layer, the lower-center punch is slid down. The upper-center punch is then pulled away to make a space, which is filled with the powder for the core. This is then pre-compressed by the upper-center punch. Finally, the lower-outer punch is slid downward and the powder for the 2nd-outer layer fills and surrounds the pre-compressed core/1st-outer layer completely. The core/1st-outer layer and the 2nd-outer layer complex is then compressed by the upper and lower punches in which the center punches are unified with the outer punches, respectively. This system can be assembled onto the turn table of a rotary tableting machine, and can make a dry-coated tablet in a single turn.

A 58-year-old woman was admitted because of bilateral diffuse nodular shadows on chest radiograph. Video-assisted thoracoscopic lung biopsy specimens showed marked lymphocytic infiltration into the bronchiolar wall. HTLV-1 antibody was examined because the patient's parents were born in Okinawa Prefecture. The patient turned out to be an adult T-cell leukemia-lymphoma (ATLL) carrier with positive HTLV-1 antibody. Therefore, HTLV-1 associated bronchiolitis was diagnosed. Although no dry symptoms appeared, it became clear by the saxon test that she was also complicated with Sjögren syndrome. Generally, it is reported that there is coherence with HTLV-1 infection and Sjögren syndrome. So the HTLV-1 infection might have accounted for the pathogenesis of these three disorders (HTLV-1 infection, bronchiolitis, Sjögren syndrome).

To investigate the association between the expression of matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) and the clinicopathological features in lepidic and invasive components of adenocarcinoma of the lung, we performed immunostaining for type IV collagen, various MMPs, and TIMPs in 27 cases of invasive adenocarcinomas and 5 cases of atypical adenomatous hyperplasia of alveolar epithelial cells (AAH). Mean extent of lepidic growth was 61% and the survival was significantly better in cases with 50% or more lepidic component. The preservation of type IV collagen in lepidic areas correlated inversely with lymphatic or vascular invasion (P = 0.02 and 0.002, respectively). Five-year survival was reduced in cases showing destruction of type IV collagen (P = 0.004) or expression of MMP-2 (P = 0.008) in lepidic areas. MMP-2 co-localized with MT-1-MMP (its activating enzyme) and TIMP-2 in neoplastic cells. Reactivity for other MMPs and TIMPs did not correlate with destruction of type IV collagen or prognosis. Type IV collagen was preserved in all cases of AAH. MMP-2, but not MT-1-MMP, was expressed in two of the five cases of AAH. Immunostaining for type IV collagen MMP-2 is useful in evaluating the prognosis of the lung.

Purpose: Stereotactic radiotherapy (SRT) is highly effective for brain metastases from non-small-cell lung cancers (NSCLCs). As such, primary lesions of NSCLC may also be treated effectively by similar focal high-dose SRT. Methods and Materials: Between October 1994 and June 1999, 50 patients with pathologically proven T1-2N0 M0 NSCLC were treated by CT-guided frameless SRT. Of these, 21 patients were medically inoperable and the remainder were medically operable but refused surgery. In most patients, SRT was 50–60 Gy in 5–10 fractions for 1–2 weeks. Eighteen patients also received conventional radiotherapy of 40–60 Gy in 20–33 fractions before SRT. Results: With a median follow-up period of 36 months (range 22–66), 30 patients were alive and disease free, 3 were alive with disease, 6 had died of disease, and 11 had died intercurrently. Local progression was not observed on follow-up CT scans in 47 (94%) of 50 patients. The 3-year overall survival rate was 66% in all 50 patients and 86% in the 29 medically operable patients. The 3-year cause-specific survival rate of all 50 patients was 88%. No definite adverse effects related to SRT were noted, except for 2 patients with a minor bone fracture and 6 patients with temporary pleural pain. Conclusions: SRT is a very safe and effective treatment for Stage I NSCLC. Additional studies involving a larger patient population and longer follow-up periods are warranted to assess this new treatment for early-stage lung cancer.

The aim of this study was to evaluate the usefulness of determination of telomerase activity and expression of human telomerase RNA component (hTERC) and human telomerase reverse transcriptase (hTERT) for the diagnosis of lung carcinomas. The tissues studied consisted of 115 carcinomas and adjacent nonneoplastic lung, which were removed surgically without previous chemotherapy or radiotherapy. Telomerase activity was determined using a semiquantitative polymerase chain reaction-based telomeric repeat amplification protocol (TRAP) assay. The results obtained were classified into high and low telomerase groups. Localization of expression was examined by using in situ hybridization and immunohistochemistry. The correlation between telomerase activity in lung carcinoma and clinicopathologic features, including prognosis, was investigated. Telomerase activity in lung carcinomas was detected in 107 of 115 (93%) lung carcinomas, but not in any adjacent noncancerous tissues, and was significantly higher in small cell carcinoma than in any other histologic type. This activity also was significantly higher in poorly differentiated than in well-differentiated squamous cell carcinomas and adenocarcinomas. The overall survival rate (P =.020) was significantly lower in the high telomerase group. Messenger RNAs for hTERC and hTERT were mainly detected in the cytoplasm of cancer cells by in situ hybridization, and TERT protein was localized in the nuclei of these cells by immunohistochemical staining. Determinations of telomerase activity by in situ hybridization, immunohistochemistry, and TRAP assay are useful for evaluating the diagnosis and prognosis of lung carcinomas. H UM P ATHOL 32:188-195. Copyright © 2001 by W.B. Saunders Company

The aim of this study was to further clarify the role of the cell-associated isoform of vascular endothelial growth factor (VEGF189) on tumour growth and vascularity. Five isoforms of VEGF have been identified with different biological activities. VEGF121, VEGF145, VEGF165, VEGF189, VEGF206 are generated by alternative splicing. We used a hammerhead-type ribozyme (V189Rz) to suppress VEGF189 mRNA. The V189Rz specifically cleaved exon 6 of VEGF189 mRNA, but showed no activity against the VEGF121 or VEGF165 isoforms. The V189Rz was introduced into the human non-small cell lung cancer (NSCLC) cell line (OZ-6/VR). The expression level of VEGF189 mRNA was decreased in the OZ-6/VR cells, while VEGF121 and 165 expression was unaltered. The OZ-6/VR cells xenotransplanted into nude mice showed markedly reduced vascularisation and growth, whereas the cell line did not show any decreased growth under tissue culture conditions. The OZ-6/VR cells (1 x 10(5) cells/mouse) formed no tumours, whereas the parental OZ-6 cells formed large tumours within 8 weeks. The specific suppression of VEGF189 by the ribozyme decreased vascularity and xenotransplantability of the lung cancer cell line. Thus, the cell-associated isoform of VEGF, VEGF189, might have a key role in stromal vascularisation and the growth of NSCLC xenografts in vivo.

The Noguchi criteria are useful in assessing the prognosis of patients with small lung adenocarcinoma. Although there is a significant difference in prognosis between type A or B and type C, it is difficult in some cases to distinguish these types accurately by microscopy. In this study, we used immunohistochemistry to examine alpha-smooth muscle actin (alpha-SMA) produced by active fibroblasts in 25 pulmonary adenocarcinomas less than 2 cm in diameter. Eleven of type C (61%) showed positive staining for alpha-SMA, whereas no positive cases were seen in type A or B. The incidence of cancerous blood vessel and lymphatic invasion were significantly higher in alpha-SMA positive cases than in negative cases, and the positive cases showed poorer prognosis. These findings indicate that immunohistochemical detection of alpha-SMA is useful and essential for histological typing by the Noguchi criteria.

Multidrug resistance-associated protein (MRP) is one of the major factors responsible for non-P-glycoprotein (Pgp)-mediated multidrug resistance of human tumour cells. In this study, we examined MRP and aberrant p53 expression in 54 colorectal cancers (CRC), 35 carcinoma in adenomas (CIA) and 40 adenomatous polyps by immunohistochemical procedures. 38 of 54 (70%) CRCs, 16 of 35 (46%) CIAs and 3 of 40 (8%) adenomatous polyps were MRP positive (chi 2 test, P0.0001). 36/54 (67%) CRCs, 10/35 (29%) CIAs and 0/40 adenomatous polyps were p53 positive. 30 of the 36 p53-positive CRCs were also MRP positive and 8/10 CIAs were both p53 and MRP positive. MRP overexpression correlated with aberrant p53 accumulation in CRCs and CIAs (chi 2 test, P= or 0.01). Coexpression of MRP and p53 in the same cells was confirmed in the CRCs and CIAs by double staining procedures. These results suggested that MRP overexpression is related to aberrant p53 expression in CRC.

E-Selectin is an inducible adhesion molecule, which is expressed on cytokine-activated endothelial cells and is thought to interact with cancer cells to initiate metastases. The relationship between serum E-selectin levels and prognoses in 101 patients with resected non-small cell lung cancers (NSCLCs) was studied, and survival curves were compared in relation to E-selectin levels and expression of two carbohydrate antigens, Sialyl Lewisx (SLX) and Sialyl Lewisa (CA19-9), which were immunohistochemically detected in resected specimens in 65 of the 101 cases. The serum E-selectin level on admission was 48.9+/-25.7 ng/ml (mean+/-SD, n=101), and the E-selectin-positive rate was 22.7%, being correlated with the progression of T-factor. The high E-selectin group showed a significantly worse survival rate than the normal E-selectin group. Multivariate analysis confirmed the significant prognostic value of E-selectin. The mean postoperative E-selectin level in 52 cases (36.93 ng/ml) was significantly lower than the preoperative E-selectin level (43.57 ng/ml), indicating that certain NSCLCs might induce the expression of E-selectin. In cases expressing carbohydrate antigens (SLX, CA19-9), the high E-selectin group showed a significantly worse survival curve than the normal E-selectin group. On the other hand, there was no significant difference in the survival curve between the high and normal E-selectin groups when carbohydrate antigens were negative. These results suggest that patients who have high serum E-selectin levels, especially with carbohydrate antigen-positive NSCLC, might be expected to have poor prognoses.

Indications for thoracoscopic metastatectomy remain controversial because not all metastatic tumors may be detected without the manual palpation that is possible with thoracotomy. However, the accuracy (92%) of preoperative lung imaging in patients with one or two lesions led us to re-evaluate thoracoscopic metastatectomy with patient survival as the primary end point. Thoracoscopic wedge resection using an endoscopic stapling device or video-assisted thoracic surgery (VATS) lobectomy was performed in patients with one or two pulmonary metastases. Thoracoscopic resection was performed in 27 patients with 22 solitary lesions and 5 patients with two lesions. The primary tumors were colorectal cancer (15), testicular cancer (3), osteosarcoma (2), and seven other histologies. In 5 of 27 patients (18.5%) a thoracoscopic operation was converted to a VATS procedure, which requires minithoracotomy to identify metastasis primary by digital palpation. The 3-year survival rate for colorectal cancer patients who underwent thoracoscopic resection was 56.4%, in comparison to 48.6% in historical control thoracotomy patients (n = 16). There was no statistically significant difference between the two groups. Thoracoscopic resection of one or two colorectal cancer lung metastases results in a survival rate similar to standard thoracotomy, and thereby provides an acceptable alternative to this more invasive approach.

We examined whether the increased expression of P-glycoprotein (P-gp) encoded by the human multidrug resistance gene MDR1 is related to the acquired multidrug resistance of lung cancer in vivo. We estimated the chemosensitivity of lung cancer xenografts (LC-6, adenocarcinoma; Lu-24, small-cell cancer) by calculation of relative tumour growth (T/C%, treated/control) in vivo, based on statistical significance determined by the Mann-Whitney U test (P < 0.01, one-sided). MDR1 gene expression levels were evaluated by reverse transcription-polymerase chain reaction (RT-PCR) assay. P-gp production and P-gp localisation were examined by Western blotting and by immunohistochemical analysis respectively. LC-6 and Lu-24 were initially sensitive to both vincristine (VCR, 1.6 mg kg-1: LC-6, 45%; Lu-24, 39%) and doxorubicin (DOX, 12 mg kg-1: LC-6, 26%; Lu-24, 27%) in vivo. VCR-resistant variants (LC-6R, 66% and Lu-24R, 68%) selected with VCR (0.4 mg kg-1, x 9) significantly acquired cross-resistance to DOX (LC-6R, 55% and Lu-24R, 55% respectively). RT-PCR assay showed increased levels of MDR1 expression in LC-6R and Lu-24R with stable MDR1 expression levels. P-gp expression levels were elevated, and the percentage of P-gp-positive tumour cells increased in both LC-6R and Lu-24R. These results suggest that P-gp/MDR1 overexpression is related to acquired multidrug resistance in lung cancer in vivo. Images Figure 3 Figure 4 Figure 5

Background The altered and anomalous expression of carbohydrate antigens (CA) occur in patients with lung carcinomas. Methods To investigate the relationship between prognosis and immunohistochemical findings of CA in serum and pulmonary adenocarcinomas (PA), PA specimens surgically resected from 102 patients were studied with the use of A, B, H, Lewis(Le)a, Le(b), Le(x), Le(y), sialyl Le(a) (FH-7), sialyl Le(x-i) (SLX) (FH-6), sialosyl Tn (TKH-2), and CA 19-9. The Lewis blood group types were determined by the dot blotting method on patients' serum using monoclonal anti-Le(a), Le(b), Le(x), and Le(y). Formalin-fixed paraffin-embedded PA sections were stained using the avidin-biotin-peroxidase complex methods. Results There was no correlation between the patients' postoperative survival and tissue expression of CA, although survival correlated with the clinical stages, histologic differentiation of PA, and serum SLX in Stage 4. The higher the positive rate of both Le(b) and Le(y), the better their differentiation in PA specimens. Regardless of blood group type, PA showed high positive reactions for FH-6 (88%) and Le(y) (87%). The serum concentration of CA 19-9 correlated with immunohistochemical reactions of tumors (Spearman correlation coefficient = 0.33, P = 0.02). The expression of Le(a) in Lewis (a-b+) phenotype patients and Type 2 CA, such as Le(y) and FH-6, is characteristic in PA. Conclusions The findings suggest that CA tissue expression may not reflect postoperative survival length of patients with PA, but biological aberrant fucosylation or sialylation as well as morphologic alteration may occur in neoplastic cells.

Production of cathepsin B by tumor cells has been linked to metastatic potential in several experimental models. Sections of 95 primary lung adenocarcinomas were examined for expression of cathepsin B using a standard avidin-biotin immunohistochemical technique. Staining for cathepsin B was observed in 22.1% of all cases and 28.0% of those of the Clara cell type. In Clara cell adenocarcinomas, cathepsin B expression correlated with positive lymph node status, presence of distant metastases, and poor prognosis (P < 0.05). However, no correlation with clinical outcome was observed in other cell types. Our data suggest that cathepsin B may be involved in invasion and metastasis in Clara cell lung adenocarcinoma.

Bronchopleural fistula is one of the most severe complications of lung operations. To prevent bronchopleural fistula, we modified the stapling technique to include folding of both sides of the cartilaginous main bronchus. This reduces the tension at the center of the membranous portion of the airway. From 1991 to 1994, this technique was performed in 7 patients. Despite the fact that 4 of these patients received adjuvant therapy, none had development of a bronchopleural fistula.

An anterior mediastinal tumor containing suture thread was suspected histologically of being an old hematoma.A 53-year-old male was found to have an abnormal shadow in the right chest field on a routine examination. He had had a right middle lobectomy for pulmonary tuberculosis 32 years previously. A block resection of the mass was carried out for the anterior mediastinal tumor. The tumor measured 6. 5 × 4. 5 ×3. 2 cm, and had a fibrous capsule surrounding a necrotic and hemorrhagic mass. Histological examination of the specimen revealed an old hematoma containing suture thread with calcification. There was no evidence of inflammation, tuberculosis or neoplasm.We considered that the tumor might be the result of chronic bleeding of unknown etiology, related to the former operation.