Indo-Oceanic Mycobacterium tuberculosis strains from Thailand associated with higher mortality.

SETTING: This study was conducted among tuberculosis (TB) patients in a highly endemic Thai province.OBJECTIVE: To evaluate the association between different Mycobacterium tuberculosis lineages and clinical characteristics, especially mortality.DESIGN: We enrolled 1,304 TB patients registered from 2002-2011 with culture isolates whose lineages were identified by specific regions of deletion. Data on mortality within 1 year of follow-up were extracted from the registration system and hospital records. Mortality-associated risk factors, including bacterial lineages, as independent variables were analysed using Cox regression models.RESULTS: Of 1,304 isolates, 521 (40.0%) and 582 (44.6%) belonged to Indo-Oceanic and East-Asian lineages, respectively. Indo-Oceanic strains significantly increased the mortality risk compared with East-Asian strains (adjusted hazard ratio [aHR] 1.42, 95%CI 1.02-1.99) or modern lineages (aHR 1.49, 95%CI 1.08-2.06) in the 172 patients who died within 1 year after TB diagnosis. The former also caused significantly higher mortality than modern lineages among patients who died within 6 months after TB diagnosis (aHR 1.62, 95%CI 1.12-2.35). No significant association was found between drug resistance and death.CONCLUSION: In Thailand, the Indo-Oceanic lineage of M. tuberculosis increased mortality risk compared with modern lineages or the East-Asian lineage, the latter being considered highly virulent in previous studies.

Accuracy of composite diagnostic standards for pneumococcal pneumonia in vaccine trials.

Because of a lack of gold standard diagnostics, a combination of multiple diagnostic tests, or composite diagnostic standard, has been used to measure pneumococcal pneumonia (PP) in pneumococcal vaccine trials. We estimated the accuracy of composite diagnostic standards for PP used in previous randomised controlled trials by simple formulas. A systematic literature review identified five eligible trials and all trials had used different combinations of diagnostic tests for PP. The estimated values of sensitivity and minimum specificity of composite diagnostic standards varied substantially between trials: 48.4% to 98.1% and 71.0% to 97.3%, respectively. Without standardizing the outcome measurements, pneumococcal vaccine efficacy estimates against PP are not comparable between trials and their pooled estimates are biased.

Risk factors of symptomatic NSAID-induced small intestinal injury and diaphragm disease.

BACKGROUND: The aetiology for nonsteroidal anti-inflammatory drug (NSAID)-induced small intestinal injuries has not been well characterised. AIM: To determine the risk factors of symptomatic NSAID-induced small intestinal injuries, including diaphragm disease. METHODS: Of the 1262 symptomatic patients who underwent videocapsule endoscopy and/or double-balloon enteroscopy, 156 consecutive patients were verified as having taken NSAIDs. Their CYP2C9*2, *3 and *13 single nucleotide polymorphisms (SNPs) were determined by allelic discrimination with Taqman 5'-nuclease assays. RESULTS: Of the 156 NSAIDs users, 31 patients (20%) were diagnosed with NSAID-induced small intestinal injury. Multivariate analysis indicated that the presence of comorbidities and the use of oxicams (meloxicam, ampiroxicam and lornoxicam) or diclofenac were associated with an increased risk of NSAID-induced small intestinal injury (adjusted OR: 2.97, 95% CI: 1.05-8.41, P = 0.041 and adjusted OR: 7.05, 95% CI: 2.04-24.40, P = 0.002, respectively). The combination of aspirin and non-aspirin NSAID was more damaging than aspirin alone. Age, sex, concomitant use of proton pump inhibitors, indications for NSAIDs use, duration of NSAIDs use and CYP2C9*2, *3 and *13SNPs were unrelated. The use of meloxicam and CYP2C9*3SNPs were significantly associated with an increased risk for diaphragm disease (adjusted OR: 183.75, 95% CI: 21.34-1582.38; P < 0.0001 and adjusted OR: 12.94, 95% CI: 1.55-108.36, P = 0.018, respectively). CONCLUSION: The use of specific NSAIDs and the factors interfering with NSAIDs metabolism might associate with small intestinal injury, especially with diaphragm disease.

Endoscopic diagnosis of follicular lymphoma with small-bowel involvement using video capsule endoscopy and double-balloon endoscopy: a case series.

The aims of this study were to compare the detection rates of gastrointestinal follicular lymphoma lesions by video capsule endoscopy (VCE) and double-balloon endoscopy (DBE), and to determine the pathologic diagnostic yields of DBE-directed biopsies. A total of 27 consecutive patients were enrolled. No significant difference in detection rates was observed in 12 patients who underwent total enteroscopy at both VCE and DBE. Pathologic diagnostic yields stratified by location were 91 % in the proximal duodenum at esophagogastroduodenoscopy, 88 % in the jejunum at antegrade DBE, 52 % in the ileum at retrograde DBE, and 57 % in the terminal ileum at colonoscopy. VCE and DBE were helpful in determining treatment in 44 % of patients.

Role of endoscopic ultrasonography in predicting the response to cyclosporin A in ulcerative colitis refractory to steroids.

BACKGROUND AND AIMS: Although cyclosporin A has been reported to be effective in the treatment of severe ulcerative colitis, factors predicting its therapeutic efficacy remain unclear. Technical progress in endoscopic ultrasonography has improved visualisation of the structure of the colon wall. Here, to assess the value of endoscopic ultrasonography in predicting the response to cyclosporin A treatment, we evaluated the therapeutic effect of cyclosporin A by determining the pre- and post-cyclosporin A thickness of the mucosal layer in the rectum using endoscopic ultrasonography with an ultrasonic catheter probe. PATIENTS AND METHODS: Fifteen ulcerative colitis patients who did not respond to high-doses of corticosteroids were treated with cyclosporin A by continuous intravenous infusion at 4mg/kg/day for 20 days. Before and 20 days after cyclosporin A therapy, clinical disease activity was assessed using clinical activity index scores. Colonoscopy and endoscopic ultrasonography were undertaken before and 20 days after cyclosporin A therapy. RESULTS: Following treatment with cyclosporin A, nine patients showed a decrease in clinical activity index score by six points or more and were defined as responders, while the other six were defined as non-responders. Endoscopic ultrasonography measurement using an ultrasonic catheter probe showed that thickness of the rectal mucosal layer before cyclosporin A was significantly greater in responders than in non-responders (p<0.05). Further, thickness after cyclosporin A was statistically decreased (p<0.01) in the responders but not in the non-responders. CONCLUSIONS: The ultrasonic catheter probe may represent a useful means of predicting and evaluating the efficacy of cyclosporin A treatment in severely ill ulcerative colitis patients.

Significance of tumor recurrence before pulmonary metastasis in pulmonary metastasectomy for soft tissue sarcoma.

BACKGROUND: Resection for pulmonary metastasis from soft tissue sarcomas is an accepted method for treatment, but it is still debatable which patients will benefit from surgical intervention. To find an entity of patients benefiting from pulmonary metastasectomy, we reviewed our institutional experience. METHODS: Between 1990 and 2007, 23 patients with pulmonary metastases from soft tissue sarcomas underwent complete pulmonary resection. All patients had obtained locoregional control of their primary tumors. Various perioperative variables were investigated retrospectively to confirm the role of pulmonary metastasectomy and to identify possible prognostic factors for survival after metastasectomy. RESULTS: Overall survival rate after metastasectomy was 43% and 29% at 5 and 10 years, respectively. Disease-free survival rate was 9% at 1 year after pulmonary resection. On multivariate analysis, no tumor recurrence (neither locoregional recurrence nor extrapulmonary metastasis) before pulmonary metastasis provided a significantly favorable overall survival (P=0.038). In addition, repeat metastasectomy for recurrent pulmonary metastasis also provided a favorable overall survival (P=0.041). CONCLUSIONS: Our data suggested that patients most likely to benefit from pulmonary metastasectomy for soft tissue sarcoma have no tumor recurrence before pulmonary metastasis. Furthermore, patients with repeat metastasectomy for recurrent pulmonary metastasis also presented a significantly longer survival.

Clinical features of surgical resection for pulmonary metastasis from breast cancer.

BACKGROUND AND OBJECTIVES: Metastatic breast cancer has been defined as a systemic disease. The discussion concerning the resection of lung metastases in patients with breast cancer is controversial. To confirm the role of resection of pulmonary metastases from breast cancer and to identify possible prognostic factors, we reviewed our institutional experience. METHODS: Between 1991 and 2007, 41 patients with pulmonary metastases from breast cancers underwent complete pulmonary resection. All patients had obtained or had obtainable locoregional control of their primary tumors. Various perioperative variables were investigated retrospectively to confirm the role of metastasectomy and to analyze prognostic factors for overall survival after metastasectomy. RESULTS: All patients were female with a median age of 55 years (range, 35-81 years). The overall survival rate after metastasectomy was 51% at 5 and 10 years. On multivariate analysis, fewer than four pulmonary metastases and a disease-free interval of more than 3 years were significantly favorable prognostic factors for overall survival (p=0.023 and 0.024, respectively). CONCLUSIONS: The current practice of pulmonary metastasectomy for breast cancers in our institution was well justified. Pulmonary metastasectomy in patients with previous breast cancer might be justified when fewer than four pulmonary metastases or a disease-free interval of more than 3 years.

[Mediastinal aberrant goiter; report of a case].

A 54-year-old woman was admitted to our hospital because of an abnormal shadow on chest X-ray. Chest computed tomography (CT) scan and magnetic resonance imaging (MRI) demonstrated an anterior mediastinal tumor. The tumor was resected completely through a median sternotomy. The tumor was dissected successfully from the surrounding vessels in spite of the heavy adhesion to them. The blood supply of the tumor was from a branch of the brachiocephalic artery. The tumor was 9 x 8 x 3 cm in size, and was diagnosed as an aberrant mediastinal goiter since it showed no communication to the thyroid gland. An aberrant mediastinal goiter is a quite rare entity of diseases and its removal through the neck would result in uncontrolled blood loss because its blood supply usually derives from intrathoracic vessels.

Confocal endomicroscopy for the diagnosis of gastric cancer in vivo.

BACKGROUND AND STUDY AIMS: Advances in endoscopy have led to imaging of the details of the gastric mucosa, but the histological diagnosis usually has to be confirmed by endoscopic biopsy. A method of confocal endomicroscopy that has recently been developed allows the observation of living cells in vivo. Several investigators have reported that the technique is of value, but there have as yet been no studies describing its application in gastric cancer. PATIENTS AND METHODS: Twenty-seven patients with early gastric cancer underwent confocal endomicroscopy (Pentax EG-3870CIK; Pentax, Tokyo, Japan). After intravenous administration of fluorescein sodium, confocal images obtained from the normal mucosa and from cancerous lesions were interpreted by two pathologists independently and compared with the histological findings, including CD34 immunostaining of biopsy specimens or resected specimens from the same sites. RESULTS: Fluorescein yielded high-quality confocal images of the gastric mucosa; if cancer could be targeted (59%) images were mostly graded good. The images corresponded to the hematoxylin-eosin staining of transverse sections of specimens from the same sites. In the results for the interpretation by the two pathologists, the accuracy for the diagnosis of gastric cancer was 94.2% (pathologist A), and 96.2% (pathologist B), respectively. The accuracy decreased substantially when poor images and inaccessible lesions were included. CONCLUSIONS: Confocal endomicroscopy is useful in the diagnosis of gastric cancer but good quality images cannot always be obtained. In the future, it may allow virtual biopsy and help reduce unnecessary biopsies.

Melanoma differentiation-associated gene-7 (mda-7)/interleukin (IL)-24 induces anticancer immunity in a syngeneic murine model.

Previous studies have shown that the human melanoma differentiation-associated gene-7 (mda-7)/interleukin-24 (IL-24) has tumor-suppressor activity in vitro and in vivo. Additionally, in vitro studies using human peripheral blood mononuclear cells indicate that mda-7/IL-24 has TH1 cytokine-like activity. However, the individual properties of mda-7/IL-24 have been previously examined separately. Thus, there is not a single study that has examined both, antitumor and proimmune properties of mda-7/IL-24. Furthermore, the tumor suppressive activity and the cytokine activity of mda-7/IL-24 have not been previously tested in an immunocompetent setting. We therefore in the present study evaluated the antitumor and immune properties of mda-7/IL-24 in a murine syngeneic tumor model. In vitro, adenovirus-mediated mda-7 gene (Ad-mda7) transfer to murine fibrosarcoma (UV2237m; MCA16) and normal (10T1/2) cells significantly inhibited growth (P=0.001) and induced apoptosis in tumor cells but not in normal cells. In vivo, intratumoral administration of Ad-mda7 resulted in significant inhibition of tumor growth (P<0.05), with a subset of mice showing complete tumor regression. We next evaluated the immune potentiation activity of Ad-mda7 in a cancer vaccine model. UV2237m cells transfected with Ad-mda7 and injected into syngeneic immunocompetent C3H mice were unable to grow; however, they did grow in immunocompromised nude mice. These tumor-free C3H mice, when challenged with parental tumor cells experienced no tumor growth, suggesting induction of systemic immunity. Moreover, splenocytes prepared from vaccinated C3H mice demonstrated higher proliferative activity and produced elevated levels of TH1 cytokines compared with those from control mice. An in vitro subset analysis of splenocytes from vaccinated mice demonstrated a significant increase in the CD3(+)CD8(+) but not the CD3(+)CD4(+) cell population (P=0.019). Thus Ad-mda7 treatment of syngeneic tumors induces tumor cell death and promotes immune activation, leading to anticancer immunity.

Preliminary comparison of capsule endoscopy and double-balloon enteroscopy in patients with suspected small-bowel bleeding.

BACKGROUND AND STUDY AIMS: Capsule endoscopy (CE) and double-balloon enteroscopy (DBE) have been introduced as modalities for examining the entire small bowel. The aim of the present study was to assess the clinical effects of CE and DBE to consider the roles of CE and DBE and the indications for the procedures in patients with suspected small-bowel bleeding. PATIENTS AND METHODS: Between June 2004 and January 2005, 32 patients in whom a site of bleeding in the gastrointestinal tract had not been identified were enrolled in the study. Twenty-eight patients were examined with both methods. Bleeding sources were categorized as either A1 lesions (immediate hemostatic procedures required) or A2 lesions (close observation required). CE and DBE were evaluated with regard to whether or not they were capable of accessing the entire small bowel and provided a diagnosis, and the access and diagnostic rates were calculated. RESULTS: On CE, 13 patients were diagnosed with A1 lesions and six with A2 lesions; on DBE, 11 had A1 lesions and one had an A2 lesion. The access rate for the entire small intestine on CE was 90.6 % (29 of 32), significantly higher than with DBE at 62.5 % (10 of 16; P < 0.05). The diagnostic rate on CE was 59.4 % (19 of 32), higher than with DBE at 42.9 % (12 of 28; P = 0.30), but not significantly different. Among patients with A1 lesions who were diagnosed with DBE, histological diagnoses were obtained in six of the 11, and three patients were treated. CONCLUSIONS: In many suspected small-bowel bleeding cases, CE should be selected for the initial diagnosis and DBE for treatment or histopathological diagnosis after detection of the bleeding site on CE.

Quantitative analysis of the microvascular architecture observed on magnification endoscopy in cancerous and benign gastric lesions.

BACKGROUND AND STUDY AIMS: Gastric cancer remains a common malignant tumor in Japan. The aim of this study was to attempt a quantitative evaluation of the microvascular architecture observed by magnification endoscopy using image analysis, and to investigate whether this method is able to distinguish between gastric cancers and benign lesions. PATIENTS AND METHODS: A total of 132 patients were studied using magnification endoscopy, and image analysis was performed in 71 patients (32 patients with early gastric cancer, 39 patients with benign lesions). Analysis was not possible in the other 61 patients because the quality of the image was not good enough. A square region of interest was selected from the magnified images of the gastric mucosa. From this we extracted the vascular images corresponding to microvessels and calculated the mean caliber of vessels in the region of interest. RESULTS: Image analysis provided good-quality images of microvessels and enabled evaluation of the microvascular architecture. The mean caliber of vessels was 4.454 pixels in 17 differentiated adenocarcinomas, 4.319 pixels in 15 undifferentiated adenocarcinomas, and 4.034 pixels in the 39 benign lesions. This represented a significant difference between gastric cancers and benign lesions (P<0.0001). Histopathological investigation of surgically resected tumors demonstrated the mean caliber of microvessels in cancerous lesions to be greater than that of microvessels in the surrounding mucosa. CONCLUSIONS: Image analysis was useful for evaluating the microvascular architecture of the gastric mucosa, and calculation of the mean caliber of the vessels may prove helpful in the differential diagnosis of gastric cancers. However, analysis was not possible in 61 of the 132 patients studied because of inadequate image quality, and this represents a significant limitation of this diagnostic method.

UFT inhibits lung metastases in spontaneous metastasis model of lung cancer.

BACKGROUND: UFT, an oral 5-fluorouracil derivative, is the only drug that is effective as a postoperative adjuvant therapy for non-small cell lung cancer (NSCLC) [ ], but the mechanism of the action remains unclear. We examined whether UFT and/or its metabolite, gamma-hydroxybutyric acid (GHB) inhibits lung metastases in a mouse model. METHODS: Lewis lung carcinoma cells were implanted into the foot pads of C57 BL/6 mice, and mice were treated with UFT or GHB. RESULTS: Both the mean number of metastatic nodules and the mean lung weight for UFT-treated mice (11.4 and 192.1 mg, respectively) were significantly lower than those for saline-treated mice (41.5 and 415.0 mg, respectively) (p < 0.001 for both). UFT did not inhibit tumor growth at the primary sites (foot pads). No significant body weight loss was documented in UFT-treated mice. GHB did not inhibit development of lung metastases even when a higher dose was used. CONCLUSIONS: UFT inhibits development of lung metastases without any toxicity in mouse model, which may explain the efficacy of postoperative administration of UFT for resected NSCLC.

The use of endoscopic ultrasound-guided fine-needle aspiration for investigation of submucosal and extrinsic masses of the colon and rectum.

BACKGROUND AND STUDY AIM: Ensdoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) has been reported as a useful technique for histological diagnosis of submucosal or extrinsic gastrointestinal and pancreatic lesions. The aim of this study was to evaluate the use of EUS-FNA for the diagnosis of lesions either within or adjacent to the wall of the colon and rectum. PATIENTS AND METHODS: A total of 22 patients with a lesion within the wall of, or adjacent to, the colon or rectum underwent EUS-FNA. They were divided into two groups: patients who had previously had a malignancy (the "previous +ve" group, n = 11), and patients who had not previously had a malignancy (the "previous -ve" group, n = 11). In the four patients who had lesions located proximal to the sigmoid colon, EUS-FNA was performed using a guide wire and overtube. The success rates for adequate tissue sampling and for detecting malignant and benign masses by EUS-FNA were evaluated and the success rate for detection was compared with the success rate of EUS and computed tomography. RESULTS: Sufficient tissue for evaluation was obtained from 21 of the 22 patients (95.5 %). The overall rate of detection of malignant and benign masses was 95.5 % (21/22) for EUS-FNA and 81.8 % (18/22) for pre-EUS-FNA imaging investigations. Of the 11 patients in the previous +ve group, ten were diagnosed with recurrences of primary malignancies; of the 11 patients in the previous -ve group, four were diagnosed with primary malignancies and seven were diagnosed with benign lesions. There were no complications related to the EUS-FNA procedure. CONCLUSIONS: EUS-FNA is a safe technique which is useful in the planning of treatment for patients who have a mass within the wall or adjacent to the wall of the entire length of the colon or rectum.

A new method of segmental resection for primary lung cancer: intermediate results.

OBJECTIVE: To improve the postoperative results of limited resection for small lung cancer, we have developed a new operative method, pulmonary artery-guided segmentectomy. This resection begins with identification of the pulmonary arterial branches involved in the tumor, then the pulmonary tissue is divided along the pulmonary arteries (i.e. guided by pulmonary arteries) from the hilum toward the periphery by electrocautery. The advantages of this method include the facilitation of securing adequate margin from the tumor, and the feasibility of intralobar lymph node dissection during operation. To examine the efficacy of the new method of segmental resection, we retrospectively reviewed 74 cases of T1N0M0 disease who underwent the pulmonary artery-guided segmentectomy. METHODS: From 1993 to 2000, 74 patients with pathological T1N0M0 lung cancer were treated by the pulmonary artery-guided segmentectomy. Forty-one patients (55.4%) who underwent the segmentectomy had been considered suitable candidates for lobectomy (intentional resection group). The other 33 patients (44.6%) were considered poor candidates for lobectomy because of poor cardiopulmonary reserve (compromised resection group). RESULTS: The overall survival rate at 5 years was 82.0%. The 5-year survivals in the intentional and the compromised resection groups were 81.6 and 77.6%, respectively, and no significant differences were detected between the groups. According to tumor size, the 5-year survival rate for patients with tumors of 20 mm or smaller (92.9%, n=53) was higher than that for the patients with tumors of 21-30 mm (63.0%, n=21), but the difference did not reach statistical significance. Median follow-up time of 27.0 months revealed eight locoregional recurrences and four deaths due to lung cancer. Sixty-three patients (85.1%) are alive with no evidence of disease, and six patients (8.1%) are alive with recurrent disease. Locoregional recurrences occurred in one of 53 patients (1.9%) with tumors 20 mm or smaller and in seven of 21 patients (33.3%) with tumors 21-30 mm, the difference being statistically significant (P<0.01). CONCLUSIONS: Our intermediate results demonstrated that the new pulmonary artery-guided segmentectomy could be an alternative method for selected patients with small lung cancer, particularly with tumors 20 mm or smaller in diameter.

Evaluation of angiogenesis in non-small cell lung cancer: comparison between anti-CD34 antibody and anti-CD105 antibody.

PURPOSE: Angiogenesis is an essential process in the progression of malignant tumors. Whereas pan-endothelial markers, such as CD34, are generally used in evaluation of angiogenesis, pan-endothelial antibodies react with not only "newly forming" vessels but also normal vessels just trapped within tumor tissues. It has been recently reported that anti-CD105 antibody preferentially reacts with "activated" endothelial cells in angiogenic tissues. Thus, the superiority of anti-CD105 monoclonal antibody (mAb) in evaluation of angiogenesis of non-small cell lung cancer (NSCLC) was assessed. EXPERIMENTAL DESIGN: A total of 236 patients with resected NSCLC were retrospectively reviewed. Intratumoral microvessel density (IMVD) was determined with an anti-CD34 mAb (CD34-IMVD) and with an anti-CD105 mAb (CD105-IMVD). RESULTS: The mean CD34-IMVD and CD105-IMVD were 179.9 and 41.6, respectively. Whereas CD34-IMVD was significantly correlated with the expression of vascular endothelial growth factor (P = 0.003), CD105-IMVD was more closely correlated with vascular endothelial growth factor expression (P < 0.001). The 5-year survival rate of the lower CD105-IMVD patients was 74.9%, significantly higher than that of the higher CD105-IMD patients (60.4%, P = 0.018). Whereas the 5-year survival rate of the lower CD34-IMVD patients seemed higher than that of the higher CD34-IMVD patients (63.7%), the difference did not reach a statistical significance (P = 0.137). Multivariate analysis confirmed that higher CD105-IMVD was a significant factor to predict poor prognosis (P = 0.029), whereas CD34-IMVD was not (P = 0.070). CONCLUSIONS: Anti-CD105 mAb proved to be superior to anti-CD34 mAb in evaluation of angiogenesis in NSCLC.

Addition of ATP and MgCl2 to the preservation solution attenuates lung reperfusion injury following cold ischemia.

BACKGROUND: In lung transplantation, reperfusion injury following cold ischemia is one of the crucial problems for recipients. OBJECTIVE: We evaluated the protective effect of adding a combination of ATP and MgCl2 to the preservation solution against lung reperfusion injury following cold ischemia. METHODS: Using an isolated rat lung perfusion model with fresh rat blood as the perfusate, the rats were divided into five groups (n = 6). In the fresh group, the study lungs were flushed with phosphate-buffered saline (PBS), then immediately reperfused for 120 min. In the control group, the study lungs were flushed with PBS, then cold ischemia was induced for 9 h (4 degrees C), after which reperfusion was performed. In the other three groups, the protocols were the same as for the control group except that ATP and/or MgCl2 were added to the PBS: ATP group (100 microM ATP), MgCl2 group (100 microM MgCl2) and ATP + MgCl2 group (100 microM ATP + 100 microM MgCl2). RESULTS: In the ATP + MgCl2 group, the intrapulmonary shunt fraction, peak airway pressure and wet to dry lung weight ratio were significantly lower than those in the control group. No improvement was observed in the ATP or MgCl2 groups. Histological examination supported these physiological results. In all groups, flush time and lipid peroxide levels in the lungs after cold ischemia did not show any significant differences. CONCLUSION: The addition of ATP and MgCl2 to the preservation solution attenuated reperfusion injury following cold ischemia in rat lungs.

Prognostic factors in patients with resected pathologic (p-) T1-2N1M0 non-small cell lung cancer (NSCLC).

OBJECTIVES: To clarify prognostic factors in resected pathologic (p-) T1-2N1M0 non-small cell lung cancer (NSCLC). METHODS: A total of 95 consecutive patients who underwent complete tumor resection and mediastinal dissection for pT1-2N1M0 NSCLC between 1976 and 1997 were retrospectively reviewed. p53 status and proliferative activity were evaluated immunohistochemically. RESULTS: The extent of N1 stations and p53 status proved to be significant prognostic factors. The 5-year survival rate for tumor without hilar node (#10) involvement was 66%, significantly higher than that for tumor with #10 involvement (39%, P<0.01). The 5-year survival rate for tumor with aberrant p53 expression was 37%, significantly lower than that for tumor without aberrant p53 expression (74%, P<0.01). There proved to be no significant difference in the prognosis between pT1 disease and pT2 disease; the 5-year survival rates for pT1 and pT2 diseases were 62 and 56%, respectively. Age, gender, performance status, grade of tumor differentiation, histological type, or proliferative activity were not significant factors. Multivariate analysis of prognostic factors using Cox's proportional hazard model confirmed these results. CONCLUSIONS: Involvement of the hilar node and aberrant p53 expression were significant factors to predict a worse prognosis in resected T1-2N1M0 NSCLC.

Expression of neural cell adhesion molecules (polysialylated form of neural cell adhesion molecule and L1-cell adhesion molecule) on resected small cell lung cancer specimens: in relation to proliferation state.

BACKGROUND AND OBJECTIVES: Alteration of homotypic cell-cell adhesion has been suggested to play an important role in tumor progression. The present study examined the relationship between neural cell adhesion molecules and state of proliferation of small cell lung cancer (SCLC) cells. METHODS: Seventeen surgically resected specimens of SCLC were immunohistochemically examined, by using monoclonal antibodies against neural cell adhesion molecule (NCAM) and its polysialic acid side chains, and L1 cell adhesion molecule (L1-CAM). Ki-67 labeling indices were also determined immunohistochemically. RESULTS: All patients were positive for L1-CAM. Fifteen patients (88.2%) were positive for NCAM. Among the fifteen patients, nine (60.0%) were positive for NCAM PSA side chain. The probability of survival of the NCAM without PSA side chain group was significantly higher than that of the NCAM with PSA side chain group (log-rank test; P = 0.500). CONCLUSIONS: The expression of NCAM with PSA side chains might be a prognostic factor and NCAM a marker for SCLC. L1-CAM may be synthesized independent of state of proliferation of individual tumor cell and may affect clinical feature of SCLC.

Prognostic significance of polysialic acid expression in resected non-small cell lung cancer.

Polysialic acid (PSA) is a carbohydrate attached mainly to the neural cell adhesion molecule. Because PSA is composed of a linear homopolymer of alpha-2-8-linked sialic acid residues and has a large negative charge, the presence of PSA attenuates the adhesive property of neural cell adhesion molecule and increases cellular motility. In an earlier study, we demonstrated that PSA and STX, a polysialyltransferase, were associated with tumor progression in non-small cell lung cancer (NSCLC) (F. Tanaka et al., Cancer Res., 60: 3072-3080, 2000). Therefore, in the present study, to assess the prognostic significance of PSA in resected NSCLC, a total of 236 patients who underwent complete resection for pathological (p)-stage I-IIIa disease were reviewed retrospectively. PSA was expressed in 44 of 236 (18.6%) patients, and the expression was correlated with p-stage disease. For all p-stage patients, 5-year survival rates for those with PSA-positive and PSA-negative tumors were 52.1% and 71.3%, respectively, demonstrating a significantly worse prognosis for the PSA-positive patients (P = 0.012). Analysis for only p-stage I patients also demonstrated a significantly worse prognosis for the PSA-positive patients; 5-year survival rates of the PSA-positive and the PSA-negative patients were 45.1% and 83.5%, respectively, (P < 0.001). In addition, there proved to be no difference in the postoperative survival among p-stage I, II, and IIIa patients when PSA expression was positive. Multivariate analysis confirmed that PSA expression was an independent factor to predict poor prognosis in resected NSCLC. These results suggested that PSA could be an important clinical marker and that preoperative induction and/or postoperative adjuvant therapies should be performed for PSA-positive NSCLC, even if the disease is classified as p-stage I.