Search

OBJECTIVES Although segmentectomy is an acceptable alternative to lobectomy for peripheral small-sized non-small-cell lung cancer, the effectiveness of segmentectomy for inner lesions remains unknown. The aim of this study was to examine the feasibility of segmentectomy in comparison with lobectomy for inner lesions. METHODS We retrospectively analysed 570 patients with small (≤2 cm) cN0 non-small-cell lung cancer who underwent segmentectomy or lobectomy between January 2007 and March 2021. We focused on patients with lesions located in the inner two-thirds, which were determined using three-dimensional computed tomography (n = 227). After propensity score matching analysis based on sex, age, pulmonary function, serum carcinoembryonic antigen level, radiographic tumour findings and tumour location, we compared the surgical and oncological outcomes in patients who underwent segmentectomy (n = 66) and lobectomy (n = 66). RESULTS Postoperative mortality or morbidity did not differ significantly between the 2 groups. The 5-year recurrence-free and overall survival rates in the segmentectomy and lobectomy groups were 93.6% vs 84.1% and 95.8% vs 87.9%, respectively. The differences between 2 groups were not significant (P = 0.62 and P = 0.23, respectively). The 2 groups also showed no differences in loco-regional recurrence. Multivariable Cox regression analysis revealed that segmentectomy had a comparable impact on recurrence-free survival (hazard ratio, 0.61; 95% confidence interval, 0.17–2.03; P = 0.43). CONCLUSIONS Segmentectomy for inner-located small-sized non-small-cell lung tumours could be an acceptable treatment in comparison with lobectomy.

Background and Objectives: There have been numerous advances in spine surgery for metastatic spinal tumors, and minimally invasive spine stabilization (MISt) is becoming increasingly popular in Japan. MISt is a minimally invasive fixation procedure that temporarily stabilizes the spine, thereby reducing pain, preventing pathological fractures, and improving activities of daily living at an early stage. MISt may be useful given the recent shift toward outpatient cancer treatment. Materials and Methods: This study enrolled 51 patients with metastatic spinal tumors who underwent surgery using MISt between December 2013 and October 2020. The Spinal Instability Neoplastic Score, an assessment of spinal instability, was used to determine the indication for surgery, and the Epidural Spinal Cord Compression scale was used for additional decompression. Results: The patients comprised 34 men and 17 women, and the mean age at surgery was 68.9 years. The mean postoperative follow-up period was 20.8 months, and 35 of 51 patients (67%) had died by the last survey. The mean operative time was 159.8 min, mean blood loss was 115.7 mL, and mean time to ambulation was 3.2 days. No perioperative complications were observed, although two patients required refixation surgery. Preoperatively, 37 patients (72.5%) were classified as Frankel grade E. There were no cases of postoperative exacerbation, and six patients showed improvement of one or more Frankel grades after surgery. The median duration of patient survival was about 22.0 months. Patients with breast, prostate, renal, and thyroid cancers had a good prognosis, whereas those with gastrointestinal and head and neck cancers had a poor prognosis. Conclusions: MISt can benefit patients who are ineligible for conventional, highly invasive surgery and is also suitable because cancer treatment is increasingly performed on an outpatient basis. Furthermore, choosing the right surgery for the right patient at the right time can significantly affect life expectancy.

Acute exacerbation (AE) of idiopathic pulmonary fibrosis (IPF) is among the most fatal postoperative complications of lung resection in patients with IPF. Non-small-cell lung cancer (NSCLC) with IPF exhibits basal segment dominance. Treatment options for these lesions include lobectomy or basal segment segmentectomies. However, these procedures potentially increase risks of AE due to surgical stress including prolonged operative time and loss of pulmonary function. Therefore, as an alternative to these procedures, we developed a simple and practical deep wedge resection technique for basal segments. Our technique is minimally invasive and quick and simple approach in patients with NSCLC and IPF.

Advances in cancer treatment helped in increasing the life expectancy of patients with cancer. However, a concomitant increase in the number of patients with bone metastases can be expected. A new multidisciplinary treatment strategy for patients with metastatic spinal tumors was designed, and has been practiced from 2013 in our hospital. The benefits of liaison treatment for metastatic spinal tumors is useful for early detection and early treatment before the collapse of the stabilization mechanism and the appearance of neurological symptoms, and enables team medical care by various experts. This system is a useful treatment for metastatic spinal tumors, because it enables radiotherapy and/or surgery before the onset of skeletal related events(SRE)and will also help maintain the activities of daily living(ADL)and quality of life(QOL)for patients with metastatic spinal tumors.

A 73-year-old man visited his family doctor with complaints of cough and breathlessness. Right pleural effusion was detected by chest X-ray. Computed tomography(CT) showed a huge mass 13×11 cm in the right mediastinum along with right pleural effusion and atelectasis of the right middle and lower lobes. Surgery was performed 4 days after admission. Although the tumor was huge, it could be successfully removed. The symptoms improved and the patient was discharged after 10 days of surgery. Pathological examination revealed vagal nerve schwannoma with no malignant features.

Aim We examined the advantages of thoracoscopy over thoracotomy in terms of perioperative outcomes and toleration of adjuvant chemotherapy. Methods Between April 2010 and March 2013, 657 patients with non-small-cell lung cancer who underwent lobectomy were classified into thoracoscopy (308 patients) and thoracotomy (349 patients) groups and compared. Results The thoracoscopy group had less blood loss compared to the thoracotomy group ( p Conclusions These results indicate that totally thoracoscopic lobectomy is the more beneficial surgical approach with regard to the incidence of postoperative complications and toleration of adjuvant chemotherapy.

Positive pleural lavage cytology (PLC) findings are considered to be predictive of a poor prognosis in patients with non-small-cell lung cancer (NSCLC). We investigated the clinical benefit of adjuvant chemotherapy for lung adenocarcinoma patients with positive PLC findings.We retrospectively reviewed the medical records of lung adenocarcinoma patients who underwent tumour resection and had positive PLC findings between January 2000 and December 2009.Fifty-three patients (4.8%) of 1114 patients with lung adenocarcinoma had positive PLC findings. The median follow-up period was 33.6 months. Adjuvant chemotherapy was administered to 24 patients (adjuvant chemotherapy group); 7, 8 and 9 patients had pathological Stage I, II and III, respectively . The surgery-alone group comprised 29 patients; 12, 8 and 9 patients had pathological Stage I, II and III, respectively. The 5-year recurrence-free survival (RFS) rates were 34.6 and 15.7% (P0.01) in adjuvant chemotherapy and surgery-alone groups, respectively. The rate of distant recurrence was significantly reduced in the adjuvant chemotherapy group (25.0 and 58.6%; P = 0.01). Even for Stage I cases, adjuvant chemotherapy tended to improve the 5-year RFS rate compared with surgery alone (60.1 and 29%; P = 0.11). Multivariate analysis for RFS revealed that adjuvant chemotherapy [hazard ratio (HR), 0.45; P = 0.03], tumour size30 mm (HR, 2.23; P = 0.02) and lymph node metastasis (HR, 2.67; P0.01) were significant independent prognostic factors for recurrence.Adjuvant chemotherapy for lung adenocarcinoma patients with positive PLC findings significantly improved recurrence-free survival.

Objectives We evaluated the clinical benefit of segmentectomy for patients with cT1bN0M0 lung cancer. Methods We retrospectively reviewed the medical records of 178 patients who underwent lobectomy or segmentectomy for cT1bN0M0 lung adenocarcinoma and squamous cell carcinoma from January 1995 to December 2005. We investigated the association of surgical outcomes with the presence of pathological invasion. Results The median follow-up period was 93.4 months. Of 178 patients, 37 were scheduled for segmentectomy, but 6 of these patients were switched to receive lobectomy due to surgical N1 or N2 in 3 patients and insufficient surgical margins in 3 patients. In total, 31 patients underwent segmentectomy, and 147 underwent lobectomy. The 5-year overall survival (OS) was similar between the patients who underwent lobectomy (5-year OS, 81.6%) and segmentectomy (5-year OS, 77.4%, P = 0.73). Among pN0 patients without pathological invasion, there was no difference in OS between patients who underwent lobectomy (5-year OS, 89.9%) and segmentectomy (5-year OS, 88.9%, P = 0.80). In contrast, among pN0 patients with pathological invasion, OS was greater in patients who underwent lobectomy (5-year OS, 80.9%) than in those who underwent segmentectomy (5-year OS, 54.6%; P = 0.19). Moreover, a significantly higher rate of local and local + distant recurrence was observed in patients who underwent segmentectomy (45%) than in those who underwent lobectomy (15%) in this group (P = 0.02). Conclusions The results of our study suggest that segmentectomy may not be recommended for cT1b tumours if pathological invasion is suspected before surgery.

Objective Pulmonary large cell neuroendocrine carcinoma is a rare high-grade malignant tumor. Because large cell neuroendocrine carcinoma is rare, the optimal treatment, including perioperative chemotherapy, has not been defined. We retrospectively analyzed the correlation among the effectiveness of perioperative chemotherapy in treating large cell neuroendocrine carcinoma, pathologic stage, and immunoreactivity to neuroendocrine markers. Methods A total of 63 patients with pulmonary large cell neuroendocrine carcinoma undergoing surgical resection from 2001 to 2009 were included. The resected tumors were immunohistochemically stained with the 3 neuroendocrine markers synaptophysin, chromogranin A, and neural cell adhesion molecule. We categorized patients who were positive for all 3 markers as the triple-positive group and those who were negative for 1 or 2 markers as the non–triple-positive group. Results Perioperative chemotherapy resulted in better overall survival than surgery alone ( P = .042). Multivariate analysis of survival revealed that perioperative chemotherapy was a significant independent prognostic factor (hazard ratio, 0.323; 95% confidence interval, 0.112-0.934; P = .0371). Among the patients who received perioperative chemotherapy, the non–triple-positive group had a significantly greater 5-year survival rate than the triple-positive group ( P = .0216). Moreover, among the non–triple-positive group, a significantly greater 5-year survival rate was observed for the patients who underwent surgery with chemotherapy than for those who underwent surgery without chemotherapy ( P = .0081). In contrast, no difference was found in 5-year survival between patients with chemotherapy and those without chemotherapy when the tumors were triple positive. Conclusions Our results suggest that perioperative chemotherapy might benefit the survival of patients with pulmonary large cell neuroendocrine carcinoma, in particular when the tumors are not immunoreactive to all 3 neuroendocrine markers.

We focused on OGG1 Ser326Cys, MUTYH Gln324His, APEX1 Asp148Glu, XRCC1 Arg399Gln, and XRCC3 Thr241Met and examined the relationship between the different genotypes and survival of Japanese lung cancer patients. A total of 99 Japanese lung cancer patients were recruited into our study. Clinical data were collected, and genotypes of the target genes were identified by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Survival analysis to verify the impact of these gene polymorphisms on the clinical outcome of lung cancer showed that lung squamous cell carcinoma patients with the Thr/Met genotype at XRCC3 had a significantly shorter survival time than those with the Thr/Thr genotype (13 months versus 48 months, log-rank test, p &lt, 0.0001). Cox regression analysis showed that the carriers of XRCC3 genotypes were at a significantly higher risk [adjusted hazard ratio (HR) = 9.35, 95% confidence interval (CI) = 2.52–34.68, p = 0.001, adjusted HR = 9.05, 95% CI = 1.89–44.39, p = 0.006]. Our results suggest that XRCC3 Thr241Met may act as a favorable prognostic indicator for lung squamous cell carcinoma patients.

Introduction The significance and handling of microscopic invasion of non-small cell lung cancer (NSCLC) into hilar peribronchovascular soft tissue (SHEATH+) have not been defined in the TNM classification by AJCC/UICC; nevertheless, SHEATH+ may be equivalent to spread into the mediastinum. Also, assessment of the margin of peribronchial resection is challenging because of the technical difficulty of inking, and intraoperative and postoperative artifacts. Methods Records of 592 consecutive Asian patients with primary NSCLC (excluding adenocarcinoma in situ) who had, without any preoperative therapy, undergone lobectomy, sleeve lobectomy and pneumonectomy were examined. SHEATH+, simply defined as invasion of hilar peribronchovascular soft tissue, without categorizing any invasive patterns, and its significance were statistically analyzed. Results Forty-four SHEATH+ cases demonstrated significantly advanced TNM stages, and were statistically associated with central occurrence, pN1-3, and vascular invasion, as assessed by logistic regression analysis. No statistically significant differences were observed between TNM stage-adjusted frequency of recurrence and recurrence-free intervals. Kaplan–Meier's estimates of the rate of overall and recurrence-free survival after surgery showed no statistically significant differences between SHEATH+ and SHEATH−. Cox's multivariate analysis suggested SHEATH was not a statistically independent prognostic factor under the TNM classification by AJCC/UICC (7th edition). Conclusions SHEATH+ in NSCLC was simply associated with central occurrence and advanced TNM stages. To the best of our knowledge, this is the first report on the significance of SHEATH+ in NSCLC.

Angiosarcoma is a rare neoplasm, accounting for only 1%-2% of all sarcomas. It occurs most frequently in the skin and soft tissue and rarely in the thoracic region. To our knowledge, a mediastinal angiosarcoma is extremely rare. We report on the surgical resection of a rare case of giant epithelioid angiosarcoma originating in the anterior mediastinum, followed by six courses of adjuvant chemotherapy (doxorubicin + ifosfamide). The patient is alive and asymptomatic 1 year after surgery. As the prognosis for unresectable cases is generally dismal, surgical resection and adjuvant therapy can be an option for mediastinal angiosarcoma.

The GINS complex associates with cell division cycle (Cdc) protein 45 and mini-chromosome maintenance (Mcm) proteins 2-7 to form the Cdc45-Mcm-GINS (CMG) complex, which is essential for DNA duplication. One member of the GINS complex is Psf3. We previously found that increased Psf3 expression was strongly associated with poor survival in lung adenocarcinoma. Here, we investigated the role of Psf3 expression in non-small-cell lung cancer (NSCLC). We verified Psf3 expression in human NSCLC tissues (180 patients) and cell lines. Immunohistochemical analysis revealed that the overexpression of Psf3 was significantly associated with vessel invasion (P = 0.016), lymphatic invasion (P = 0.002), and pleural invasion (P = 0.036). The overall survival rate in patients with Psf3 overexpression was significantly lower than that in patients without Psf3 overexpression (P = 0.006). Multivariate survival analysis revealed Psf3 expression to be an independent risk factor for an unfavorable outcome (P = 0.049). A proximal ligation assay showed interactions between Psf3 and other CMG components (such as Mcm2 and Cdc45) in both NSCLC specimens and cell lines, indicating that Psf3 acted as the CMG complex, which could lead to excessive proliferation. Knockdown of Psf3 inhibited the proliferation of both cell lines by delaying the S phase, which revealed that Psf3 played an important role in cancer proliferation. Thus, Psf3 acted as the CMG complex, promoting excessive proliferation. These results suggest that Psf3 inhibition might be a therapeutic target for NSCLC with Psf3 overexpression.

Objective: We prospectively evaluated the efficacy of water seal in the management of air leak after pulmonary resection. Methods: Eighty-seven patients who underwent lobectomy were enrolled. Air leak was qualitatively described on each postoperative day using a six-grade scale. All chest tubes were continuously suctioned at a negative pressure of 12 cm H2O until the morning of postoperative day (POD) 1. Switch was made to water seal if the air leak was graded as “minor at expiration” or lower. This procedure is referred to as “the water seal challenge”. Results: On POD 1, 58 patients had air leaks. The water seal challenge was attempted on POD 1.6±1.0. While 45 patients (78%) continued to receive the water seal, the remaining 13 patients were switched to suctioning at −5 cm H2O followed by the successful second water seal challenge within 3 days from the first challenge. The air leak stopped 3.1±3.0 days after the application of the water seal in the 58 patients. None of the following correlated with the duration of air leak: preoperative pulmonary function tests, type of lobectomy, age, and gender. Only the leak grade on POD 0 correlated significantly with the duration of air leaks (p

ObjectiveDifferentiation of bronchioloalveolar carcinoma from other subtypes of lung adenocarcinomas is important in the preoperative assessment of patients. We examined the biologic aggressiveness of small-sized adenocarcinomas according to the pathologically defined bronchioloalveolar carcinoma degree and its correlation with computed tomography findings. In addition, we attempted to predict which patients were suitable for a lesser resection.MethodsOf 424 consecutive patients who underwent operation for primary lung cancer in the last 3 years, 114 with a histopathologically proven adenocarcinoma 3 cm or less in diameter underwent complete removal of the primary tumor. We examined the characteristics of patients classified into 3 groups based on the proportion of the bronchioloalveolar carcinoma component: 0% to 20% (n = 40), 21% to 50% (n = 38), and 51% to 100% (n = 36). We also investigated the correlation of the bronchioloalveolar carcinoma component with computed tomography findings such as ground-glass opacity (defined as a hazy increase on the lung window) and tumor shadow disappearance rate (defined as the ratio of the tumor area of the mediastinal window to that of the lung window).ResultsMale gender (P = .0001), advanced pathologic stage (P = .001), larger size of the tumor (P = .004), nodal involvement (P = .04), pleural invasion (P = .0003), lymphatic invasion (P = .002), and vascular invasion (P = .0002) were observed more often among patients with a smaller proportion of bronchioloalveolar carcinoma. A positive and significant correlation was found between the rate of bronchioloalveolar carcinoma component and ground-glass opacity (R2 = 0.488, P < .0001) and tumor shadow disappearance rate (R2 = 0.727, P < .0001). As an independent predictor of nodal status, tumor shadow disappearance rate (P = .015) and bronchioloalveolar carcinoma component (P = .015), as well as tumor size, were significantly valuable, although ground-glass opacity proportion (P = .086) was marginally informative.ConclusionsSmall-sized adenocarcinomas with a greater ratio of bronchioloalveolar carcinoma component showed less aggressive behavior. Both tumor shadow disappearance rate and ground-glass opacity ratios, which are obtained preoperatively, were well associated with bronchioloalveolar carcinoma ratios, which are determined postoperatively. Furthermore, tumor shadow disappearance rate had a stronger impact as a predictor of bronchioloalveolar carcinoma component. Preoperative assessment of tumor shadow disappearance rate may be useful to identify patients requiring a less extensive pulmonary resection.

BACKGROUND There remains ongoing controversy with regard to the optimal management strategy and the prognostic significance of small-sized nonsmall cell lung carcinoma. Therefore, in the current study, the authors analyzed the clinical characteristics of patients who underwent complete resection of these lung tumors, the follow-up data, and the significant prognostic factors. METHODS Of 1726 consecutive patients surgically treated for proven primary lung carcinoma, 265 patients underwent complete removal of a nonsmall cell lung carcinoma in which the greatest dimension of the resected specimen was ≤ 2 cm. RESULTS The cancer-specific 5-year and 10-year survival rates were 86% and 83%, respectively. Univariate analyses revealed that advanced pathologic stage, a tumor size of 16–20 mm, lymphatic vessel invasion, vascular vessel invasion, a high serum level of carcinoembryonic antigen (CEA), and extended resection were significantly unfavorable prognostic factors. Among these factors, multivariate analyses demonstrated that pathologic stage (P < 0.0001), vascular vessel invasion (P = 0.0040), and CEA level (P = 0.0291) were significant, independent determinants of survival. None of the patients with pathologic Stage I disease, no vascular vessel invasion, and a low serum CEA level died of their disease after undergoing complete resection. CONCLUSIONS The preoperative level of serum CEA and vascular vessel invasion by tumor cells were found to be independent prognostic factors that were as significant as the well established determinant of pathologic stage for patients with a nonsmall cell lung carcinoma measuring ≤ 2 cm in greatest dimension. These data may contribute to the explanation of the lower-than-expected survival of patients after complete surgical resection of such a small-sized tumor. Cancer 2003;98:535–41. © 2003 American Cancer Society. DOI 10.1002/cncr.11530

This report introduces a hilar side approach for posterior basal segmentectomies by the process of specific vision thoracoscopic surgery, which has been used extensively for peripheral small lung cancer by the author. Although it requires a deeper understanding of hilar anatomy and fine control, it is safer and less invasive to the thoracic wall and results in less postoperative pain than the thoracotomy counterpart and as a hilar side approach allows for less deformation. The necessary order of processes involves specific vision, inflation-deflation and blunt dissection from the hilum.

Background Lung cancer is one of the leading causes of cancer death worldwide. Even with complete resection, the prognosis of early-stage non-small cell lung cancer is poor due to local and distant recurrence, and it remains unclear which biomarkers are clinically useful for predicting recurrence or for determining the efficacy of chemotherapy. Recently, several lines of evidence have indicated that the enzymatic activity of cyclin-dependent kinases could be a clinically relevant prognostic marker for some cancers. We investigated whether the specific activity of cyclin-dependent kinases 1 and 2 could predict recurrence or death in early non-small cell lung cancer patients. Methods Patients with newly diagnosed, pathologically confirmed non-small cell lung cancer were entered into this blinded cohort study. The activity of cyclin-dependent kinases was determined in 171 samples by the C2P® assay, and the results were subjected to statistical analysis with recurrence or death as a clinical outcome. Results The Cox proportional hazards model revealed that the activity of cyclin-dependent kinase 1, but not 2, was a predictor of recurrence, independent of sex, age, and stage. By contrast, cyclin-dependent kinase 2 activity was a predictor of death, independent of sex and stage. Conclusion This study suggested the possible clinical use of cyclin-dependent kinase 1 as a predictor of recurrence and cyclin-dependent kinase 2 as a predictor of overall survival in early-stage non-small cell lung cancer. Thus, a combination of activity of cyclin-dependent kinases 1 and 2 is useful in decision-making regarding treatment strategies for non-small cell lung cancer after surgery. Electronic supplementary material The online version of this article (doi:10.1186/1471-2407-14-755) contains supplementary material, which is available to authorized users.

DNA repair enzymes play an important role in the development of various kinds of cancer. We here analyzed associations of XPD Lys751Gln, APEX1 Asp148Glu, XRCC1 Arg399Gln, and XRCC3 Thr241Met gene polymorphisms in DNA repair pathways in relation to the risk of lung cancer using PCR-RFLP. The study involved 104 lung cancer patients and 120 non-cancer controls divided into non-smokers and smokers. We found a statistically significant interaction between APEX1 Asp148Glu and the risk for lung cancer (adjusted OR 2.78, 95% CI 1.58-4.90, p=0.0004), of both adenocarcinoma (adjusted OR 2.24, 95%CI 1.18-4.25, p=0.014) and squamous cell carcinoma (adjusted OR 4.75, 95%CI 1.79-12.6, p=0.002) types. XRCC1 Arg399Gln showed a borderline significant association with adenocarcinoma (adjusted OR 1.89, 95%CI 1.00-3.57, p=0.051). The combined effect of smoking and presence of the APEX1 Asp148Glu demonstrated a significant association with risk of lung cancer (adjusted OR 3.61, 95% CI 1.74-7.50, p=0.001). The XPD Lys751Gln and XRCC3 Thr241Met genotypes displayed no statistically significant risk. Our findings suggest that the APEX1 Asp148Glu is associated with increased risk for primary lung cancer in Japanese individuals partaking in smoking.

A simple screening method for quantitatively analyzing asbestos bodies that can be carried out even in community hospitals, is needed in order for laborers and neighborhoods in the vicinity of asbestos factories to apply for compensation for asbestos-related injury. Eighty-eight consecutive cases of surgically resected primary lung cancer were analyzed for asbestos bodies using two methods, and the correlation between them was statistically examined. The first was the conventional technique using lung tissue digestion and phase-contrast scanning, and the second was the authors' method using light microscopy to scan the sediment of formalin-injected lung specimens. The overall correlation coefficient of the concentration of asbestos bodies between the authors' method (C(AB/SED)) and the conventional method (C(AB/DLT)) was 0.4576, a weak statistically significant correlation; in patients with occupational asbestos exposure, however, the correlation coefficient was 0.7341. Despite the cost, it may be prudent to use the conventional method under the present law for patients with C(AB/SED)>or=3.5/mL. C(AB/DLT) >3000/g dry lung tissue when C(AB/SED) is >or=3.5/mL suggests the potential for the accumulation of asbestos absorption by lung tissue.

We reported on 34 patients with superior sulcus non-small-cell lung cancer and clinical outcome. It is necessary to select the most appropriate approach from preoperative examination and the degree of infiltration at the chest wall. Recently, various approach and preoperative chemoradiotherapy followed by surgical resection is effective for the treatment of superior sulcus tumor (SST), we should keep challenging for radical resection in mind.

A 15-year-old boy was admitted with a pneumothorax of the left lung. Computed tomographic scans demonstrated a tumor 20 mm in diameter situated on the left main to upper lobar bronchus that eventually was proved to be a typical carcinoid tumor by transbronchial biopsy. We performed bronchial resection with atypical bronchoplasty, which preserves lung parenchyma in cases of s-T1N0M0 disease. The patient has had no evidence of recurrence 7 years after surgery.

Reduced expression of connexins (Cxs), gap junction proteins, is frequently reported in malignant cell lines and tumors, whereas recent studies suggested that C x 26, a subtype of Cxs, might help tumor cells acquire malignant phenotypes. To examine this suggestion in the clinical setting, 50 lung squamous cell carcinomas (SCCs) were stained with the anti-C x 26 antibody. No C x 26-specific signals were detectable in 34 tumors (group I; 68%), whereas the remaining 16 were judged positive for C x 26 (group II; 32%). In 14 tumors of group II, C x 26-specific signals were detected not in all SCC cells but in SCC cells facing the tumor stroma or capsule, in which the signals were localized on the plasma membrane. Involved lymph nodes of group-II patients often contained metastatic foci consisting of all C x 26-positive cells. The proportion of C x 26-positive to C x 26-negative SCC cells in the metastatic nodes was larger than that in the corresponding primary tumors. C x 26-positive SCC cells seemed to be more invasive and metastatic than negative ones. Consistently, the 5-year cancer-specific survival rate of group-II patients was significantly lower than that of group-I patients (12.5 vs 38.9%; P=0.0391). Multivariate analysis demonstrated that C x 26 expression (P=0.0448) as well as pathological stage (P=0.0338) and vascular invasion (P=0.0191) were independent, significant prognostic predictors. These results suggest that C x 26 may represent an essential effector for controlling the biological aggressiveness of lung SCC tumor.

Objective As a result of increasing discovery of small-sized lung cancer in clinical practice, tumor size has come to be considered an important variable affecting planning of treatment. Nevertheless, there have been no reports including large numbers of patients and focusing on tumor size, and controversy remains concerning the surgical management of small-sized tumors. Therefore, we investigated the relationships between tumor dimension and clinical and follow-up data, as well as surgical procedure in particular. Methods We reviewed the records of 1272 consecutive patients who underwent complete resection for non–small cell carcinoma of the lung. Results Fifty patients had tumors of 10 mm or less, 273 had tumors of 11 to 20 mm, 368 had tumors of 21 to 30 mm, and 581 had tumors of greater than 30 mm in diameter. The cancer-specific 5-year survivals of patients in these 4 groups were 100%, 83.5%, 76.5%, and 57.9%, respectively. For patients with pathologic stage I disease, they were 100%, 92.6%, 84.1%, and 76.4%, respectively. Multivariate analysis demonstrated that male sex, older age, larger tumor, and advanced pathologic stage adversely affected survival. Lesser resection was performed in 167 (52%) of 323 patients with a tumor of 20 mm or less in diameter but in 156 (16%) of 949 patients with a tumor of greater than 20 mm in diameter. The percentages of lesser resection among all procedures performed were 79%, 56%, 30%, and 15% in patients with pathologic stage I disease with a tumor of 10 mm or less, 11 to 20 mm, 21 to 30 mm, and greater than 30 mm in diameter, respectively. The 5-year cancer-specific survivals of patients with pathologic stage I disease with tumors of 20 mm or less and 21 to 30 mm in diameter were 92.4% and 87.4% after lobectomy, 96.7% and 84.6% after segmentectomy, and 85.7% and 39.4% after wedge resection, respectively. On the other hand, with a tumor of greater than 30 mm in diameter, survivals were 81.3% after lobectomy, 62.9% after segmentectomy, and 0% after wedge resection, respectively. Conclusions Tumor size is an independent and significant prognostic factor and important for planning of surgical treatment. Although lobectomy should be chosen for patients with a tumor of greater than 30 mm in diameter, further investigation is required for tumors of 21 to 30 mm in diameter. Segmentectomy should, as a lesser anatomic resection, be distinguished from wedge resection and might be acceptable for patients with a tumor of 20 mm or less in diameter without nodal involvement.

Objective Although sleeve segmentectomy for centrally located lung cancers was originally designed for patients unable to tolerate lobectomy, we have tried it in patients with noncompromised function as well. We evaluated the efficiency of this atypical type of bronchoplasty. Methods Of 202 patients for whom we performed bronchoplasty for primary non–small cell lung carcinoma, 16 underwent sleeve segmentectomy. Results Sixteen patients were classified into 4 groups according to the mode of bronchial reconstruction: type A, anastomosis between the right intermediate or left main and basal segmental bronchi with removal of the superior segment of the lower lobe (S6; n=7); type B, anastomosis between the left main and lingular bronchi with removal of the upper division of the left upper lobe (S1+2+3; n=3); type C, anastomosis between the left main and upper division bronchi with removal of the lingular segments (S4+5; n=4); and type D, others (n = 2). Nine patients had pulmonary function sufficient to tolerate lobectomy. The tumors were completely resected in all patients. Combined performance of pulmonary angioplasty was carried out in 2 patients. Bronchial reconstruction was successful in all patients, with neither bronchial complications nor local recurrences. Ten patients had stage IA disease, and 6 had more advanced disease. All patients were alive, except 1 who died as a result of distant metastasis and 2 who died of noncancerous causes. Overall 3-year and 5-year survivals were 93.3% and 68.1%, respectively. Conclusions Sleeve segmentectomy, which is technically demanding, should be considered in patients with centrally located and possibly curable early non–small cell lung cancer because the prevalence of small-sized or multiple lung tumors has been increasing and because our findings suggest that this lung-saving operation is safe and useful.

Serum carcinoembryonic antigen (CEA) has all of the properties desired for a biologic measure to be used as a prognostic indicator in the clinical evaluation of lung cancer. Carcinoembryonic antigen value appears to be related to tumor histologic type and patients' smoking status, which has yet to be intensively analyzed as reports available thus far have consisted of a limited number of patients. This study was undertaken to determine whether the prognostic value of CEA differs according to histologic type in a large group of patients with clinical early-stage lung cancer, and how smoking influences its value.Two series of 694 and 260 consecutive patients who underwent resection for clinical stage I lung adenocarcinoma and squamous cell carcinoma, respectively, were evaluated. We measured serum CEA before and after surgery, and analyzed its prognostic significance in relation to histologic type and its correlation with smoking status.We found significantly higher CEA levels in patients with adenocarcinomas than in those with squamous cell carcinomas (7.8 versus 5.5 ng/mL; p = 0.0018), but a higher percentage of CEA-positive patients among those with squamous cell carcinoma (109 of 260, 41.9%) than those with adenocarcinoma (245 of 694, 35.3%). Clinical stage I patients with a high preoperative CEA level had a poor prognosis, and for pathologically confirmed stage I patients with a high postoperative CEA level the prognosis was worse. The prognostic value of serum CEA level was thus significantly greater for adenocarcinoma than for squamous cell carcinoma. This was probably because of a much higher proportion of smokers among patients with squamous cell carcinoma. In adenocarcinoma, the growth of which was generally less influenced by smoking, the proportion of CEA-positive smokers (49.3%, 170 of 345) was greater than that of CEA-positive nonsmokers (21.5%, 75 of 349, p0.0001). Additionally, in patients with adenocarcinoma, survival of nonsmokers was more greatly influenced by CEA level than that of smokers.Although serum CEA values measured before and after surgery are important in identifying patients at high risk of poor survival, its specificity is higher for adenocarcinoma than for squamous cell carcinoma. When serum CEA levels are checked, smoking status of patients, particularly of those with squamous cell carcinoma, should be taken into account.

Background The prognostic implication of serum carcinoembryonic antigen (CEA) has yet to be comprehensively analyzed since the reports available so far have comprised small patient populations. We evaluated perioperative CEA values with regard to surgical results in a large number of patients to clarify its merit. Methods We measured serum CEA levels before and after surgery in 1,000 consecutive patients with clinical stage I non-small cell lung cancer who underwent resection of tumor. High CEA value was greater than 5.0 ng/mL. Results Three hundred and sixty-eight patients (36.8%) had high preoperative CEA levels. The CEA levels after surgery were normalized in 242 patients (24.2%) and persistently elevated in 126 patients (12.6%). High CEA levels were seen more frequently in patients with older age, male gender, larger size of tumor, incomplete resection, and advanced pathologic stage. Patients with a high preoperative CEA level had a poor survival. Among these patients, even worse survival was seen for those with a high postoperative CEA level. These prognostic trends were still observed for patients with pathologic stage I disease. Multivariate analysis demonstrated that both preoperative and postoperative CEA levels were independent prognostic determinants ( p = 0.0243 and p Conclusions Perioperative measurement of serum CEA concentrations yields information valuable for detecting patients at high risk of poor survival. Normalization of CEA levels after surgery was a significant favorable prognostic sign in patients with an elevated CEA level before surgery. Even after apparently successful surgical therapy, patients with a high CEA level should be carefully followed up, and might represent a suitable target for neoadjuvant clinical trials.

Background There have been no proven preoperative indicators for postoperative survival of patients with an adenocarcinoma, the incidence of which has been increasing lately. Methods Of 952 consecutive patients operated on for primary lung cancer between 1995 and 2002, 167 patients with a proven adenocarcinoma 3 cm or less in diameter underwent complete removal of the primary tumor. We examined their computed tomographic scans to estimate tumor shadow disappearance rate (TDR), which was defined as the ratio of the tumor area of the mediastinal window to that of the lung window, reviewed the clinical records, and evaluated their relation to prognosis. Results On univariate analyses, size of the tumor ( p = 0.0380), TDR ( p = 0.0018), carcinoembryonic antigen ( p = 0.0001) pathologic stage ( p p p = 0.0001), and vascular invasion ( p = 0.0017) were significantly associated with prognosis. Also, the outcomes of multivariate analyses for preoperative factors indicated that TDR ( p = 0.0340) and carcinoembryonic antigen ( p = 0.0047) are significant independent prognostic determinants. The 5-year survival was 48% in cases with a TDR of 0% to 25%, 87% in those with a TDR of 26% to 50%, 97% in those with a TDR of 51% to 75%, and 100% in those with a TDR of 76% to 100%. The incidence of lymphatic, vascular invasion, and nodal metastases was lower in patients with a higher TDR. Conclusions Small-sized adenocarcinomas with a higher TDR showed less lymphatic, vascular vessel invasion, or nodal involvement, and demonstrated longer survival, suggesting that TDR was associated with clinical-pathologic characteristics and tumor aggressiveness. Preoperative assessment of TDR may be useful to identify an appropriate candidate for a lesser pulmonary resection.

Background Lung cancer is still the most common cause of death due to cancer. Although the 5-year survival rate of patients with lung cancer is reported to be increasing, whether the surgical results have actually been improving or not is controversial. We reviewed our experience to evaluate time trends of surgical outcomes in patients with nonsmall cell lung cancer. Methods We reviewed the clinical records of 1,465 consecutive patients with proven primary nonsmall cell carcinoma who underwent complete removal of the primary tumor together with hilar and mediastinal lymph nodes from 1985 to 1995 (early era) and from 1996 to 2002 (late era). The clinical characteristics, surgical outcome, and overall survival of the patients were analyzed, and data from the two eras were compared. Results There were 694 patients in the early era and 771 in the late era. As for their characteristics, elder age, female sex, adenocarcinoma, earlier stage of disease and smaller size of tumor were more frequently encountered in the late era. Lobectomy was the most common procedure performed during both periods, and in the late era, the rate of segmentectomy was doubled (11% to 25%) whereas that of pneumonectomy was much less (6% to 1%). Although the frequency of operative deaths in the two eras did not differ (0.3%), that of in-hospital deaths and of postoperative complications decreased significantly in the late era (2% to 0.5% and 28% to 12%, respectively). A significant improvement in survival probability was observed in patients with pathologic stage IA ( p p = 0.0477), and III disease ( p = 0.00120) but not in those with pathologic stage II disease ( p = 0.5353). Also, the multivariate analysis of patients with pathologic stage I or III demonstrated that age, sex, and size of the tumor were significant prognostic determinants, and confirmed that the recent prolonged survivals remained significant even after simultaneous adjustment for other factors. Conclusions These data indicate a significant recent improvement in surgical outcomes after stratification of various prognostic variables although careful consideration should be given to the retrospective nature of this study.

BACKGROUND Recently, the TSLC1 (tumor suppressor in lung cancer 1) gene has been identified as a novel tumor suppressor in human nonsmall cell lung carcinoma. To the authors' knowledge, the clinical relevance of TSLC1 gene expression has not been studied using patient data and surgical samples. The current study was designed to evaluate whether the TSLC1 gene can serve as a target for the prognostic determination of patients with pulmonary adenocarcinoma. METHODS A total of 38 patients who were surgically treated for proven primary lung adenocarcinoma were enrolled in the current study. Surgical specimens were examined for TSLC1 protein expression immunohistochemically and by Western blot analysis. The correlation between levels of TSLC1 expression and pathologic characteristics, as well as prognosis, was investigated. RESULTS All patients underwent a potentially curative resection of their tumor. TSLC1 antigen expression as evaluated by immunohistochemistry was confirmed by immunoblotting. The expression of TSLC1 protein was found to be inversely correlated with advanced disease stage, lymph node involvement, lymphatic permeation, and vascular invasion. The 4-year overall survival rates of patients with a tumor demonstrating high (> 70% positive cells [n = 14 patients]), intermediate (20–70% positive cells [n = 10 patients]), and low (< 20% positive cells [n = 14 patients]) expression of the TSLC1 antigen were 84%, 28%, and 7%, respectively. In addition, the disease-free survival of patients with a tumor that demonstrated a high percentage of TSLC1 protein-positive cells was reported to be significantly better than that of patients with a tumor that showed a low percentage of TSLC1 protein-positive cells. CONCLUSIONS The loss or reduction of TSLC1 expression in resected lung adenocarcinoma cases was associated with a poor prognosis, indicating that TSLC1 represents a central effector gene for controlling the biologic aggressiveness of the tumor and that it is an essential biomarker for predicting patient prognosis. These data may help to detect those patients at high risk for recurrence who might benefit from additional therapeutic strategies such as adjuvant therapy. Cancer 2003;98:1002–7. © 2003 American Cancer Society. DOI 10.1002/cncr.11599

TSLC1 (tumor suppressor in lung cancer-1) is an adhesion molecule of the Ig superfamily that binds homophilically and mediates cell-cell interactions. Originally, TSLC1 was cloned as a candidate tumor suppressor from the genomic region that frequently exhibits loss of heterogeneity in human non-small-cell lung cancer (NSCLC). However, there have been no studies on TSLC1 expression in normal lungs or NSCLC. Here we show that pulmonary epithelial cells express TSLC1 and its expression levels are often decreased or lost in primary pulmonary adenocarcinoma, a major histologic type of NSCLC. Immunohistochemistry revealed that TSLC1 was localized at cell-cell boundaries of all columnar epithelial cells in mouse embryonic lungs of 10.5 and 13 days postcoitus. Similar staining patterns were observed in bronchiolar and alveolar epithelial cells of adult human lungs, suggesting a physiologic role for TSLC1 in interactions of these cells. Next we performed Western blot analyses of TSLC1 in 47 primary pulmonary adenocarcinomas and judged each tumor as either decreased or nondecreased by comparing TSLC1 expression levels of the tumor with the levels of normal lungs. The expression profiles had a significant relation to histologic subtypes but not to other clinicopathologic parameters. Sixteen bronchioloalveolar carcinomas (BACs) were all judged nondecreased, while 19 of 31 (63%) adenocarcinomas other than BAC were judged decreased (p < 0.0001). Immunohistochemistry of tumors judged nondecreased revealed that not only BAC cells but also tumor cells in lepidic growth components of adenocarcinomas other than BAC expressed TSLC1 on their lateral plasma membranes. These tumor cells are considered less invasive because they proliferate in a lepidic growth pattern along alveolar walls. Thus, the present results not only support the hypothesis that TSLC1 is a tumor suppressor of NSCLC but also suggest that preserved integrity of TSLC1 may contribute to less invasive phenotypes of lepidic growth tumor cells.

ObjectiveIntraoperative pleural lavage cytology for lung cancer has not been widely accepted. The prognostic significance of this procedure has yet to be intensively analyzed because the reports published thus far have involved small patient populations. We therefore performed a large prospective trial of pleural lavage cytology to elucidate its importance.MethodsCytologic status of pleural lavage fluid before any manipulation of the lung was examined in 1000 consecutive patients with non–small cell lung cancer but no pleural effusion who underwent tumor resection.ResultsForty-five (4.5%) of 1000 patients had positive cytologic findings. Positive cytologic findings were observed more frequently in patients with adenocarcinoma, advanced stage, higher involvement of lymph nodes, pleural involvement of the tumor, lymphatic permeation, vascular invasion, high level of serum carcinoembryonic antigen, and male sex. The survival rate for 5 years was 28% in patients with positive findings and 67% in patients with negative findings (P < .0001). Among 587 patients with stage I disease, 13 (2.2%) had positive findings, and their 5-year survival was 43%, which was significantly poor compared with that of patients with negative findings (81%, P = .0009). Multivariable analysis demonstrated that pleural lavage cytology was an independent prognostic determinant (P = .0290). Regarding the recurrence pattern in patients with positive findings, distant metastases (19/45 [42.2%]) were observed more frequently rather than local recurrences (19/45 [22.2%]).ConclusionsCytologic status of pleural lavage fluid immediately after thoracotomy, an independent significant prognostic factor, constitutes valuable information to detect patients at a high risk of recurrence. Therefore cytology should be performed at the time of curative resection for non–small cell lung cancer.

Objective We analyzed the long-term follow-up data on cancer-related death in 5-year survivors of complete resection of their non–small cell lung cancer and examined the prognostic factors having an impact on subsequent survival. Methods Of 848 consecutive patients with proven primary non–small cell carcinoma who underwent complete removal of the primary tumor together with hilar and mediastinal lymph nodes, 421 patients (49.6%) survived 5 years or longer after the initial surgical treatment. Of all the data analyzed, only death related to cancer was treated as death. Results The median follow-up of 5-year survivors was 84 months from the original treatment (range, 60 to 200 months). Their overall survival rate at 10 years was 91.0%. Multivariable Cox analysis demonstrated that although advanced surgical-pathological stage ( P = .0001), nodal involvement ( P = .0245), male gender ( P = .0313), and non–squamous type of the tumor ( P = .0034) were significant, independent, unfavorable prognostic determinants in all patients, none of the variables investigated significantly influenced the long-term survival of 5-year survivors. The rate of recurrence beyond 5 years was much lower compared with that within 5 years. In contrast, the rate of occurrence of new malignancies was unchanged throughout the long-term postoperative period. Conclusions Among 5-year survivors of complete resection of non–small cell lung cancer, neither stage, nodal status, sex, nor histologic condition further affected subsequent survival, suggesting that the 5-year interval might be sufficient to declare that a patient with lung cancer has been cured.