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Purpose: To investigate the effectiveness of real-time-image gated proton beam therapy for lung tumors and to establish a suitable size for the gating window (GW)., Methods and Materials: A proton beam gated by a fiducial marker entering a preassigned GW (as monitored by 2 fluoroscopy units) was used with 7 lung cancer patients. Seven treatment plans were generated: real-time-image gated proton beam therapy with GW sizes of ±1, 2, 3, 4, 5, and 8 mm and free-breathing proton therapy. The prescribed dose was 70 Gy (relative biological effectiveness)/10 fractions to 99% of the target. Each of the 3-dimensional marker positions in the time series was associated with the appropriate 4-dimensional computed tomography phase. The 4-dimensional dose calculations were performed. The dose distribution in each respiratory phase was deformed into the end-exhale computed tomography image. The D99 and D5 to D95 of the clinical target volume scaled by the prescribed dose with criteria of D99 >95% and D5 to D95 <5%, V20 for the normal lung, and treatment times were evaluated., Results: Gating windows ≤ ±2 mm fulfilled the CTV criteria for all patients (whereas the criteria were not always met for GWs ≥ ±3 mm) and gave an average reduction in V20 of more than 17.2% relative to free-breathing proton therapy (whereas GWs ≥ ±4 mm resulted in similar or increased V20). The average (maximum) irradiation times were 384 seconds (818 seconds) for the ±1-mm GW, but less than 226 seconds (292 seconds) for the ±2-mm GW. The maximum increased considerably at ±1-mm GW., Conclusion: Real-time-image gated proton beam therapy with a GW of ±2 mm was demonstrated to be suitable, providing good dose distribution without greatly extending treatment time., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Treatment of superficial tumors that move with respiration (e.g. lung tumors) using spot-scanning proton therapy (SSPT) is a high-priority research area. The recently developed real-time image-gated proton beam therapy (RGPT) system has proven to be useful for treating moving tumors deep inside the liver. However, when treating superficial tumors, the proton's range is small and so is the sizes of range straggling, making the Bragg-peaks extremely sharp compared to those located in deep-seated tumors. The extreme sharpness of Bragg-peaks is not always beneficial because it necessitates a large number of energy layers to make a spread-out Bragg-peak, resulting in long treatment times, and is vulnerable to motion-induced dose deterioration. We have investigated a method to treat superficial moving tumors in the lung by the development of an applicator compatible with the RGPT system. A mini-ridge filter (MRF) was developed to broaden the pristine Bragg-peak and, accordingly, decrease the number of required energy layers to obtain homogeneous irradiation. The applicator position was designed so that the fiducial marker's trajectory can be monitored by fluoroscopy during proton beam-delivery. The treatment plans for three lung cancer patients were made using the applicator, and four-dimensional (4D) dose calculations for the RGPT were performed using patient respiratory motion data. The effect of the MRF on the dose distributions and treatment time was evaluated. With the MRF, the number of energy layers was decreased to less than half of that needed without it, whereas the target volume coverage values (D99%, D95%, D50%, D2%) changed by less than 1% of the prescribed dose. Almost no dose distortion was observed after the 4D dose calculation, whereas the treatment time decreased by 26%-37%. Therefore, we conclude that the developed applicator compatible with RGPT is useful to solve the issue in the treatment of superficial moving tumors with SSPT.

We herein report two cases of pulmonary metastasis from renal cell carcinoma with 17-year disease-free intervals. Despite long disease-free intervals, their clinical course after pulmonary resection was different. An 82-year-old man (case 1) and a 73-year-old man (case 2), with histories of having undergone left nephrectomy for clear-cell-type renal cell carcinoma 17 years ago, were found to have right pulmonary nodules, which were detected incidentally by chest roentgenograms. A chest computed tomography revealed the presence of nodules in the right lung. They underwent surgical pulmonary resection 17 years after nephrectomy. These tumors were diagnosed as metastatic renal cell carcinoma. Currently, the case 1 patient is doing well with no signs of recurrence 42 months after pulmonary metastasectomy; however, the case 2 patient was found to have multiple tumor recurrences 11 months after metastasectomy. Their clinical courses indicate that a longer disease-free interval does not always imply a favorable prognosis.

Objective: The conventional delayed scan in dual phase of thallium-201 ((201)Tl) single-photon emission computed tomography (SPECT) is useful for estimating the viability of non-small-cell lung cancer (NSCLC). However, the influence of tumor blood flow cannot be ignored by the scan at 4 h after the tracer injection. For the purpose of improving the diagnostic capability and for clarifying the association between (201)Tl uptake and proliferative activity, we investigated the usefulness of super-delayed scan obtained at 24 h in triple-phase (201)Tl SPECT., Methods: A total of 122 patients with lung nodule, 106 of NSCLC and 16 of benign nodule, were given (201)Tl SPECT before the tumor resection. Early image (15 min), delayed image (4 h), and super-delayed image (24 h) were obtained after intravenous injection of (201)Tl chloride (111 MBq). On the each SPECT image, regions of interest (ROIs) were placed over the tumor contour (T) and contra-lateral normal lung tissue (N) area on one transverse view clearly defined lesions, and T/N ratio on the early image (ER), the delayed image (DR), and the super-delayed image (sDR), and retention indexes (RI and sRI) were calculated. All patients underwent subsequent surgical excision, and the specimens were immunostained for Ki-67 and CD34. The proliferative capability was measured as a percentage of positive nuclear area for Ki-67 (MIB-1 index). The angiogenesis was measured density of positive micro-vessels for CD34 (micro-vessel density, MVD). Correlation analysis was performed to evaluate the relationship between the MIB-1 index, MVD, and SPECT parameters., Results: The diagnostic accuracy of sDR in the differential of NSCLC was higher than that of DR (83.6% vs. 91.8%). Both DR and sDR were positively correlated with MIB-1 index. The correlation coefficient was higher in sDR (0.53 vs. 0.69). The MIB-1 index of the increasing pattern (RI < sRI) group was significantly higher (P < 0.001) than that of the decreasing pattern (RI > sRI) group., Conclusions: The super-delayed scan in the triple-phase (201)Tl SPECT is more useful than conventional delayed scan for both the diagnostic capability and assessing proliferation of NSCLC.

We presented the case of a 46-year-old man with no medical or family history but with a history of smoking 3 packs of cigarettes per day for the past 25 years. He was admitted to our hospital due to hemoptysis. Chest computed tomography revealed a tumor of right upper lung and interstitial pneumonia in the surrounding lung parenchyma. He was operated upon and diagnosed with stage IIB pleomorphic carcinoma of the lung with invasion of the chest wall. He underwent three courses of postoperative carboplatin (CBDCA) (area under the curve 5 on day 1, every 3 weeks and paclitaxel(PTX) (200 mg/m(2); day 1, every 3 weeks) combination chemotherapy. No recurrence was observed for a period of 760 days after the operation. According to previous reports, lung pleomorphic carcinoma is aggressive and has a poor prognosis. Further, the significance of chemotherapy in the management of this disease has not been established. Postoperative combination chemotherapy of CBDCA and PTX may result in a good prognosis for this disease.

Purpose: This study focused on the relationship between preoperative peripheral blood CD4(+) naïve/memory ratio and prognosis following surgery for patients with nonsmall-cell lung cancer., Methods: After measuring CD3, CD4, CD8, CD45RA, CD45RO, CD25, and intracellular CTLA4 levels, CD4(+) naïve/memory ratios were determined for 13 controls and 38 patients., Results: Although we observed no significant difference in the ratios, the patients exhibited a wider range of values than the controls. Of the 38 patients, 24 subsequently underwent surgery and were divided into three groups based on their preoperative CD4(+) naïve/memory ratio: Group I: <0.3; Group II: 0.3-0.8; and Group III: >0.8. Survival times were then evaluated. Group II survival was significantly better than Groups I and III., Conclusion: Our data suggest that the preoperative CD4(+) naïve/memory ratio may serve as a prognostic factor for nonsmall-cell lung cancer patients.

Unlabelled: We evaluated the significance of the preoperative serum C-reactive protein (CRP) level as a prognostic indicator in patients with non-small cell lung cancer (NSCLC)., Patients and Methods: Two hundred and three patients who had undergone a curative resection of NSCLC were retrospectively reviewed., Results: The proportion of the tumor size over 3 cm per patient in the CRP-positive group (> or =0.5 mg/dL: n=38) was significantly higher than that in the CRP-negative group (<0.5 mg/dL: n = 165). The proportion of the adenocarcinoma in CRP-positive group was significantly lower than that in CRP-negative group. The overall and disease specific survival rates in the CRP-positive group were significantly lower than the rates in the CRP-negative group. Based on a multivariate analysis, the preoperative serum CRP level was selected as one of the unfavorable indicators regarding survival., Conclusion: The preoperative serum CRP level is an independent and significant indicator predictive of a poor prognosis in patients with NSCLC.

Purpose: To investigate whether 201Tl uptake is associated with cell proliferation and angiogenesis in non-small-cell lung carcinoma (NSCLC)., Methods: Eighty-four patients with scheduled NSCLC underwent 201Tl single photon emission computed tomography (SPECT) imaging: 15 min (early scan) and 240 min (delayed scan) after intravenous injection of 111 MBq of 201Tl chloride. 201Tl indices were calculated on early images (early ratio: ER) and delayed images (delayed ratio: DR). The retention index (RI) was also calculated from these two parameters. Using surgically resected cancer specimens (54 adenocarcinoma, 24 squamous cell carcinoma (SCC), six large-cell carcinoma), immunohistochemical stains for both Ki-67 (MIB-1 index) and CD34 were performed to examine the proliferative activity and the micro-vessel density (MVD), respectively., Results: The mean value of 201Tl index was 1.69+/-0.77 (ER) and 2.31+/-1.08 (DR). The average RI was 42.6+/-42.9%, respectively. Both DR and RI positively correlated with MIB-1 index (r = 0.68, P < 0.05 and r = 0.52, P < 0.05). When we analyse adenocarcinoma and SCC separately, there was a significant positive correlation (r = 0.62, P < 0.05) between RI and MIB-1 index in adenocarcinoma but not in SCC (r = 0.20, P = NS). The value of ER positively correlated with MVD (r = 0.75, P < 0.05). It demonstrated strong positive correlation with both histological types (adenocarcinoma: r = 0.80, P < 0.05, SCC: r = 0.66, P < 0.05)., Conclusion: 201Tl SPECT imaging is effective non-invasive method for assessing both the proliferation and the angiogenesis in NSCLC. Both DR and RI are useful indicators for assessing cancer cell proliferation in lung adenocarcinoma. ER is a useful marker for assessing the tumour angiogenesis in NSCLC.

Background: Controversy exists regarding the relationship between serum carcinoembryonic antigen (CEA) level and T status in non-small cell lung cancer., Materials and Methods: Two hundred and forty-seven lung cancer patients with pN0 disease were included in the study and the relationship between serum CEA level and T status, tumor size and degree of local extension was investigated., Results: Patients with tumors 0 to 1.5 cm in diameter had significantly low serum CEA level. However, there were no significant differences in serum CEA level among other tumor size groups. Serum CEA level was not related to the degree of local extension. The 5-year survival of patients with both normal serum CEA levels and T1 disease was significantly better than that of patients with high serum CEA level and 72-4 disease., Conclusion: Serum CEA levels do not always relate to T status. The combined use of these factors might be useful in predicting the prognosis of pN0 non-small cell lung cancer patients.

A 75-year-old male of adenocarcinoma in non-small cell lung cancer (NSCLC) was diagnosed to be p-staged IIIA by a preoperative mediastinoscopy. After the induction chemotherapy of cisplatin (80 mg/m2, day 1, 4 weeks, 2 cycles) plus docetaxel hydrate (60 mg/m2, day 1, 4 weeks, 2 cycles), we performed lobectomy and lymph nodes dissection. The postoperative pathological results showed no metastasis of the resected lymph nodes. The postoperative stage has been down to be pN0 IA from pN2 IIIA. After the adjuvant therapy of docetaxel hydrate (60 mg/m2, day 1, 4 weeks, 2 cycles), the postoperative serum carcinoembryonic antigen level has been normalized without a recurrence for more than 2 years. A pathological staging with a mediastinoscopic diagnosis for the suspected clinical IIIA-staged NSCLC should bring us a good assessment of the induction therapy.

A small lesion showing ground-glass opacity (GGO) by preoperative computed tomography (CT) is sometimes difficult to detect after lobectomy when it locates in the central part of the lobe. In order to facilitate to identify the lesion for marking pathological specimen, we developed a new method using CT. After surgery, the resected pulmonary lobe was expanded with airflow through the bronchial stump and the target lesion was examined with CT. The laser beam of the CT on the surface of the lung is used as a guiding line for cutting. Through the application of this method for 2 clinical cases, it was found to be possible to exactly identify the GGO lesion from the surface of the resected lung enabling to visualize a fresh surface of the lesion like a CT image with minimal destruction of the structure.

Purpose: The prognosis of non-small cell lung cancer (NSCLC) with pathologic mediastinal lymph node involvement (pN2) is poor in general. The majority of previously reported prognostic factors of pN2 disease are not available preoperatively. When we perform preoperative induction chemotherapy, we should undertake therapeutic planning according to preoperative factors., Methods: We focused on preoperative clinicopathologic factors, and investigated the prognosis in 78 patients with pN2 NSCLC who received complete resection., Results: Age, gender, histologic subtype, tumor location, smoking status and cT status were not related to patients' survival. On the other hand patients with cN0 disease and normal serum carcinoembryonic antigen (CEA) level had a significant favorable survival (p = 0.038 and p = 0.019, respectively). In addition, comorbidity had a significant survival impact (p = 0.031). Despite there being no independent prognostic factors by multivariate analysis, the patients without all of cN1-2 disease, elevated serum CEA level and comorbidity had a significant favorable prognosis (p = 0.008)., Conclusion: Among the preoperative factors examined, pN2 patients with all cN0 disease, normal serum CEA level and no comorbidities might have a favorable prognosis. Combined use of these might be a useful prognostic determinant, and even in the presence of pN2 disease, patients without these unfavorable 3 factors might have a favorable prognosis when treated with surgery alone.

Background: Several reports have indicated that preoperative high serum carcinoembryonic antigen (CEA) levels are associated with poor survival after surgical resection in lung cancer., Methods: 82 consecutive lung cancer patients with preoperative high serum CEA levels (> 5 ng/mL) were included in this study. Postoperative serum CEA level was also measured. Prognostic indicators were evaluated., Results: Among patients with a preoperative high serum CEA level, a serum CEA level higher than 10 ng/mL, pT status, pN status, and positive pleural lavage cytology findings were unfavorable prognostic indicators, whereas age, gender, smoking status, histologic subtype were not. Postoperative serum CEA levels of all but 2 patients decreased, however those of 28 patients did not return to normal range. Our result showed that patients with postoperative high serum CEA level had poor prognosis. Multivariate analysis demonstrated that pT status, pN status, and postoperative high serum CEA level was an independent prognostic determinant., Conclusions: In lung cancer patients with preoperative high serum CEA levels, pT status, pN status, and normalization of serum CEA level after surgery are significant prognostic determinants.

Background: Although the prognostic significance of the serum carcinoembryonic antigen (CEA) level in non-small cell lung cancer has been reported in several studies, it is unknown whether the serum CEA level is a prognostic determinant for pN1 disease or not., Materials and Methods: Seventy patients with pN1 non-small cell lung cancer who received complete resection were reviewed. The preoperative serum CEA level was measured in all patients., Results: The pN1 patients with pT2-4 disease, hilar node involvement, multiple N1 station and elevated serum CEA level (>5 ng/mL) had a significantly unfavorable prognosis. Although a serum CEA level higher than 5 ng/mL was not an independent prognostic determinant, more than 10 ng/mL was an independent factor by multivariate analysis. In patients with pT1-2N1 disease, a serum CEA level more than 10 ng/mL was also a prognostic determinant., Conclusion: An elevated serum CEA level, especially higher than 10 ng/mL, is a significant prognostic determinant for pN1 lung cancer patients.

Background: Prognostic indicators for non-small cell lung cancer patients traditionally include TNM staging, pleural lavage cytology, and serum carcinoembryonic antigen levels. This prospective study evaluates carcinoembryonic antigen levels in pleural lavage fluid as a potential determinant for patients with lung adenocarcinoma., Methods: One hundred and fifty patients underwent thoracotomy. Pleural lavage fluid was collected, and pleural lavage cytology and lavage carcinoembryonic antigen levels were determined. The control group included 40 patients with nonmalignant disease., Results: Sixteen patients (10.7%) had positive pleural lavage cytologies. These patients and those with elevated serum carcinoembryonic antigen levels generally had a poor prognosis. Thirty-seven patients (24.7%), however, showed elevated lavage carcinoembryonic antigen levels, and a significant correlation with patient survival was demonstrated. Multivariate analysis confirmed these results. We also found a correlation between positive pleural lavage cytologies and serum carcinoembryonic antigen levels and patient survival in patients with pN0 disease but not in those with pN1-2 disease. Elevated lavage carcinoembryonic antigen levels, however, correlated significantly with survival rates in patients with pN1-2 disease., Conclusions: An elevated lavage carcinoembryonic antigen level is an independent prognostic determinant for patients with lung adenocarcinoma, even with advanced disease, and may be a more useful marker of subclinical microdissemination than pleural lavage cytology.

The disclosed 5-year survival rate for lung cancer in the Internet website represents a various difference by each institution. The better inferiority of the survival has been listed in a table to compare with other institutions and has been reported in magazines and media with a lack of an enough inspection, i.e., with a sufficient considering of a risk adjustment such as patient's background, operative policy, postoperative adjuvant therapy, and statistical background. We report our outcome of the surgical treatment for primary lung cancer. Of 875 patients treated for lung cancer in our department for 23 years between January 1980 and December 2002, 115 patients containing of 42 cases in 1997 and of 48 ones in 1992 and of 25 ones in 1987 were selected and the accumulated survival analysis was treated by Kaplan-Meier method. Eighty males and 35 females were between 15 and 80-year-old (average 63.2 +/- 11.4). The pathological classification was adenocarcinoma (n=69), squamous cell carcinoma (n=32), and others (n=14). The operative procedures were pneumonectomy (n=14), bilobectomy (n=12), lobectomy (n=85), and wedge resection (n=4). The survival time was from 29 days to 182 months (median survival time was 1471+/- 1180 days, the averaged time was 49 months). The 5-year survival rate was 41.4 +/- 9.1% (n=25) in 1987, 35.6 +/- 6.2% (n=48) in 1992, and 56.0 +/- 7.0% (n=42) in 1987, respectively (log-rank test, p = 0.2555). The 10-year survival rate was 24.1 +/- 7.9% in 1987 and 8.5 +/- 3.6% in 1992, respectively. The 5-year survival rate was as follows: IA 81.0 +/- 8.6% (n=20), IB 73.7 +/- 10.1% (n=19), IIA 57.1 +/- 18.7% (n=7), IIB 55.6 +/- 16.6% (n=9), IIIA 28.6 +/- 7.6% (n=35), IIIB 15.4 +/- 10.0% (n=13), IV 16.7 +/- 10.8% (n=12), respectively. The 5-year survival rate was as follows: male 42.8 +/- 5.3% (n=80), female 63.2 +/- 7.3% (n=35), respectively (p = 0.0147). In regard to the histological classification, the 5-year survival rate was as follows: adenocarcinoma 47.2 +/- 5.9% (n=69), squamous cell carcinoma 50.8 +/- 8.9% (n=32), respectively (p = 0.9012). As a rule of the disclosure on the internet website, we report our survival data by accompanying with minimum parameters such as, patient's background, pathological types, gender, pathological stages, and mean survival rate with standard error. When we compare the 5-year survival rate with other institutes, in considering of a risk adjustment, we would carefully have to estimate the determined survival rate with a standard error.

Objective: Although several previous studies have investigated the prognostic significance of vascular endothelial growth factor (VEGF) expression in non-small cell lung (NSCL) cancer, no previous study has concentrated on NSCL cancer with pathologically abnormal mediastinal nodes (pN2)., Methodology: A total of 60 patients with pN2 NSCL cancer who had undergone a complete resection with a systematic mediastinal lymph node dissection were reviewed retrospectively. Immunohistochemical examination, using antibodies against VEGF, was conducted. The prognostic significance of VEGF expression and clinicopathological factors were analysed., Results: The overall 5-year survival rate was 21.7%. With respect to clinicopathological factors, single N2 involvement and skip metastasis were significantly associated with patients' survival. Expression of VEGF was found in 35/60 (58.3%) patients. VEGF expression was not related to the clinicopathological parameters examined. There was no relationship between survival rates and patients positive and negative for VEGF. Multivariate analysis showed that single N2 disease was an independent prognostic factor, while VEGF expression was not., Conclusions: Although VEGF expression might be important for tumour development and maintenance, no prognostic significance of VEGF expression in pN2 NSCL cancer was found.

Background: Previously, we reported on the effectiveness of intrapleural hyperthermic perfusion with chemotherapy, a new treatment we developed for patients with malignant pleuritis. The present study analyzes the mechanism of the effectiveness of this therapy by examining the induction ratio of apoptosis among tumor cells following the perfusion treatment., Methods: This study included 11 consecutive patients with primary pulmonary adenocarcinoma and accompanying pleural seedlings and pleural effusions containing tumor cells but without distant metastasis. All patients underwent surgical resection of the primary lesion and then received sequential perfusion treatment. Tumor cells collected from the effusion both before and again at 24 hours following the perfusion treatment were subsequently examined using an immunocytochemical stain to determine apoptosis among tumor cells. The percentage of positively stained cells was expressed as the apoptotic index. We compared the survival rate of these 11 patients with the survival rate of a second group of 11 patients with malignant pleuritis who underwent surgical resection of the primary lesion but who did not receive the perfusion treatment (control group)., Results: The ratio of spontaneous apoptosis of untreated tumor cells was 2.8% +/- 2.0%. Following the perfusion, apoptosis among tumor cells was 25.2% +/- 4.6%, clearly a significant increase. While the median survival time for patients receiving the perfusion treatment was 20 months, the median survival time for the control group was 6 months., Conclusions: In patients with malignant pleuritis, intrapleural hyperthermic perfusion with chemotherapy induced potent apoptosis of tumor cells in the pleural cavity and also improved the survival rate of these patients as compared with patients who did not receive the perfusion treatment.

We investigated whether the combined use of computed tomography, thallium-201 single photon emission computed tomography and serum carcinoembryonic antigen level improves preoperative non-invasive mediastinal. 128 consecutive non-small cell lung cancer patients (85 adenocarcinomas, 31 squamous cell carcinomas and 12 others) who underwent a surgical resection were enrolled in this study. The results of the combined procedures were compared with the pathologic findings. Our results showed that the combined evaluation of mediastinal nodal involvement with the three procedures might increase underestimation, but decrease overestimation as compared to computed tomography alone. Thallium-201 single photon emission computed tomography for patients with enlarged nodes at computed tomography showed 81.3% and 100% of positive predictive value in overall and squamous cell carcinoma patients, respectively. The negative predictive value of thallium-201 single photon emission computed tomography for patients without enlarged nodes at computed tomography was highly accurate in adenocarcinoma (93.9%) as well as squamous cell carcinoma (94.4%). Combining computed tomography findings and serum carcinoembryonic antigen level had a poor predictive value. However, in patients with adenocarcinoma, a negative examination was highly accurate (95.2%). In conclusion, our results show a trend that combined use of the three procedures might improve non-invasive mediastinal staging in non-small cell lung cancer.

Background: Based on the metastatic route in lymph nodes from lung cancer, we investigated micrometastasis in the dissected lymph nodes by genetic analysis of keratin 19 and nm23-H1 (the expression of a tumor-metastatic suppressor gene) and evaluated the postoperative outcomes., Methods: Ten patients operated with lung cancer were 4 males and 6 females, who were stage IA; 2, stage IB; 3, stage IIA; 2, stage IIB; 1, and stage IIIA; 2, respectively. After total RNA extraction from the dissected lymph nodes, the expression of nm23-H1 and keratin 19 messenger ribonucleic acid (mRNA) were analyzed with reverse-transcripted polymerase chain reaction (RT-PCR)., Results: The confirmation of micrometastasis in lymph nodes was realized in seven of 10 cases (70%), in their 5-year follow-up term. In three patients there was recurrence (43%, 3/7), and the one of them had died from the mediastinal recurrence. On the expression of nm23-H1 mRNA in lymph nodes, there was no significant difference between the pathologically lymph-node metastasis positive group and the negative one, and between the group with a tumor size over 30 mm and the group with a tumor size under 30 mm, respectively. The expression ratio of nm23-H1 gene was significantly expressed in the group with micrometastasis in lymph nodes (47%, 9/19) as compared to those without micrometastasis (10%, 1/10) (p<0.05). On the all-positive expression of nm23-H1 in the examined lymph nodes (n=4), no patient had recurrence (0%, 0/4). However, in the rest of the six patients without the all-positive expression of nm23-H1 in those lymph nodes (n=6), four patients had recurrence (67%, 4/6). There was no significance between the recurrent ratio in the all-positive expression of nm23-H1 suggesting lower incidence as compared to that in patients without all-positive expression of nm23-H1., Conclusion: A detection of micrometastasis in lymph nodes could be a useful tool to identify the subpopulation of patients who might have a higher risk of recurrence and distant metastases. The nm23-H1 gene might be involved in a suppression role for micrometastasis in lymph nodes through the lymphatic route in lung cancer.

Objectives: Clinical significance of measurement of preoperative serum carcinoembryonic antigen (CEA) level in patients with non-small cell lung cancer was investigated., Methods: Consecutive 271 adenocarcinoma and 112 squamous cell carcinoma patients of non-small cell lung cancer referred to our institute were included in this study. There were 214 men and 169 women, ages ranged from 19 to 90 years, with an average of 64.46 years. Curative resection was performed for 220 adenocarcinoma and 93 squamous cell carcinoma patients. Serum level of CEA was measured before staging or resection of cancer., Results: There is a trend toward a correlation between serum CEA level and stage of the diseases, however, serum CEA level was not always related to tumor node metastasis (TNM) status. In patients with adenocarcinoma, survival rate of patients with an elevated serum CEA level was significantly lower than that with a normal serum CEA level. Multivariate analysis showed that prognostic significance of serum CEA level was TNM staging independent in patients with adenocarcinoma. On the other hand, serum CEA level was not related to patients' survival in patients with squamous cell carcinoma., Conclusions: Elevated preoperative serum CEA level is a TNM staging independent prognostic factor for patients with adenocarcinoma but not for those with squamous cell carcinoma.

Predictivity of mediastinal lymph nodes metastasis of 201Tl SPECT were examined before operation in 113 patients with non-small cell lung cancer (69 adenocarcinoma, 31 squamous cell carcinoma, 10 large cell carcinoma, 2 bronchiolo-alveolar carcinoma, 1 neuroendocrine cell carcinoma). Patients were classified into two groups, with or without lymph nodes metastasis according to the pathological diagnosis. We calculated parameters of 201Tl SPECT early ratio, delayed ratio, retention index (RI) and maximal diameters. In addition, we calculated optimal cut-off value of RI to estimate the mediastinal lymph nodes metastasis. Mediastinal lymph nodes metastasis was confirmed pathologically in 62 patients. ER and DR did not show any statistical significance between two groups. Maximal diameters of primary tumor were also comparable between two groups. RI was significantly higher in mediastinal lymph node metastasis positive group compared to that in mediastinal lymph node metastasis negative group. The sensitivity (Sen), specificity (Spe), positive predictive value (PPV), negative predictive value (NPV) and accuracy (Acc) of 201Tl SPECT were 82.2%, 82.3%, 85.0%, 79.2% and 82.3%. These parameters were similar of higher than 72.6%, 82.4%, 83.3%, 71.2% and 77.0% of chest CT. The RI of 201Tl SPECT was useful tool for predicting lymph nodes metastasis in non-small cell lung cancer. The optimum cut-off value of RI in the prediction of mediastinal lymph nodes metastasis was 35%. We should take into account of upstaging in cases with higher RI (>35%).

Aims: The prognosis of non-small cell lung cancer with pathologic mediastinal lymph node involvement (pN2) is poor, we wished to study the expression of p53, bcl-2 by immunohistochemistry in a series of such patients., Methods: Clinicopathologic factors were investigated in relation to prognosis in 60 patients with resected pN2 non-small cell lung cancer., Results: The 5-year survival rate was 21.7%. Positive staining for p53, and bcl-2 was found in 29/60 and 12/60, respectively. Patients with bcl-2 positive tumor had a more favorable survival than those with bcl-2 negative tumor (P=0.0054). The expression of p53 was not related to patients' survival. Multivariate analysis showed that Bcl-2 expression and single N2 station were independent prognostic factors., Conclusions: Patients with bcl-2 positive tumors may comprise a favorable prognostic subgroup in pN2 non-small cell lung cancer.

Metastatic tumors from various organs are found in pulmonary tissue because of the unique anatomical function of the lungs as a filter for systemic venous return. A retrospective study of the clinical factors used to assess the prognosis of 80 patients who underwent resections of metastatic pulmonary tumors in our surgical department between September 1978 and December 2002 is presented. The overall 5-year survival rate in our study was 31.7%. We demonstrated four significant factors used in predicting the prognosis of patients with resected metastatic pulmonary tumors: diameter of the tumor (3.0 cm), number of tumors (3), disease-free interval (>/=3 years or <3 years), and ratio of the diameter of the largest tumor to the diameter of the smallest tumor in patients with multiple metastases (3). Based on our results, we have applied the term "the law of 3" to these valuable prognostic factors. Among these parameters, the ratio of the diameter of the largest to the diameter of the smallest tumor may be applicable as a new prognostic parameter for surgery in patients with multiple foci. (Ann Thorac Cardiovasc Surg 2003; 9: 290-4)

Minute pulmonary meningothelial-like nodules (MPMNs), previously known as minute pulmonary chemodectomas, are relatively rare lesions. They are small (1-3 mm) and often multiple. Pathologically, they represent an interstitial nodular proliferation of small oval or spindle-shape cells arranged in a "zellenballen" nesting pattern. The function and origin of the cells are unknown. These nodules are associated with specific conditions, including thromboembolism, cardiac disease, and malignancy. We describe a patient with MPMNs and adenocarcinoma of the lung in whom HRCT showed tiny (1-3 mm in diameter) nodules of ground-glass attenuation.

A 61-year-old woman was admitted to our hospital with an abnormal shadow on chest roentgenogram. She had undergone a radical mastectomy for right breast cancer 18 years previously. Since pleural dissemination was noted at the time of thoracotomy, only tumor biopsy was performed. Although a decisive diagnosis could not be obtained histologically, the tumor resembled breast cancer and the estrogen receptor status was positive. She underwent post-operative chemotherapy and tamoxifen treatment. After tamoxifen treatment, complete response was observed. The patient is now doing well without recurrence about 10 years after thoracotomy. Based on the clinical course, we obtained both a definitive diagnosis and complete remission.

We compared the differential diagnostic capabilities of 201Tl-SPECT and biopsy methods and serum tumor marker in 125 patients with solitary pulmonary lesions composed of 87 lung cancer and 38 benign lesions. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy of 201Tl-SPECT were 76%, 95%, 97%, 63%, and 82%, respectively. These parameters are similar in biopsy methods. Although sensitivity improved to be 85% by the combination with tumor marker methods, both specificity and accuracy deteriorated to be 55% and 76%. Using combination method with 201Tl-SPECT and biopsy, sensitivity, NPV and accuracy improved to be 84%, 70% and 85%. Based on its high PPV value, 201Tl-SPECT could be useful when biopsy method could not prove lung cancer or in case whose biopsy is considered to be invasive. Because of the lower NPV value owing to false negative cases in some adenocarcinoma, negative 201Tl-SPECT case should be followed up carefully.

Objective: Although numerous studies have shown that nm23-H1 gene product expression is inversely related to metastatic potential in some cancers, the expression in lymph nodes has not been studied in detail. An analysis of nm23-H1 gene product expression in mediastinal lymph nodes from lung cancer patients is reported., Methods: One hundred and thirty-four, randomly selected lymph nodes (63 with positive pathological lymph node status) from 39 surgically treated lung cancer patients were examined. Expression of nm23-H1 gene product was determined using specific monoclonal antibodies. Metastatic cancer cells were highlighted using anti-cytokeratin antibody., Results: Expression of nm23-H1 gene product in patients with less and more than 50% nodes-positive was 12/23 (52.2%) and 15/16 (93.8%) cases, respectively. Immunohistochemical studies with cytokeratin revealed micrometastasis in 6/39 (15.4%) patients and 9/71 (12.7%) nodes previously reported as cancer negative. Expression of nm23-H1 gene product in micrometastasis and metastasis-positive nodes was 5/9 (55.6%) and 55/63 (87.3%), respectively. We also found nm23-H1 gene product expression in germinal center cells. However, we found no relationship between expression of nm23-H1 gene product in germinal center cells and extent of metastasis., Conclusions: Our study demonstrates a positive relationship between expression of nm23-H1 gene product and extent of metastasis in mediastinal lymph nodes from lung cancer patients. Our data for normal germinal center cells suggests that nm23-H1 gene product expression does not play a specific biological role in suppressing tumor metastasis in lung cancer.

Background: We conducted a retrospective study to clarify the effect of mast cells on tumor angiogenesis in lung cancer patients., Methods: Formalin-fixed and paraffin-embedded tumor sections were used in this study. Parenchymal mast cells were stained with Alcian blue and safranin O. The number of mast cells per ten fields at a magnification of 200x was counted under light microscopy, and the average count was determined. To highlight the microvessels, endothelial cells were stained with anti-human factor VIII antibody. After the microvessel count was determined, the microvessels were further stained with Alcian blue and safranin O to show areas of mast cell infiltration. Expression of vascular endothelial growth factor was assessed using a polyclonal antibody., Results: We found a significant correlation between mast cell count and microvessel density. This correlation was also observed in patients with adenocarcinoma (p < 0.001) as well as in patients with squamous cell carcinoma (p < 0.01). Double staining of the microvessels showed highly angiogenic areas densely populated with mast cells. Although we detected a slight trend toward a correlation between vascular endothelial growth factor expression and microvessel density, it was not statistically significant. We found no association between vascular endothelial growth factor expression and mast cell count., Conclusions: There appears to be a direct correlation between the number of mast cells and tumor angiogenesis in patients with lung cancer, and this relationship appears to be independent of vascular endothelial growth factor expression.

Metastatic tumors from variable organs are seen in pulmonary tissue because of its unique anatomical situation. In this article, current diagnosis and treatment for metastatic lung tumor are reviewed and discussed including recent topics. Control of metastatic lung tumor by chemotherapy and hormonal treatment has been improved. Furthermore, active applying of Video Assisted Thoracoscopic Surgery induces a change of surgical indication for metastatic lung tumor. Metastatic tumors express oncogene and tumor suppressor gene as well as primary lung cancer. However, the relationship between oncogene/tumor suppressor gene and lung metastatic phenomenon is still unclear. Molecular biological study may indicate new treatment strategy against metastatic pulmonary tumor. Prospective controlled studies for each type of primary tumor are needed to evaluate the true efficacy of pulmonary metastectomy.

Background: A retrospective study on the correlation between mast cells and survival rates of 90 pulmonary adenocarcinoma patients is reported., Methods: Surgical specimens were stained with alcian blue and safranin O, and parenchymal mast cells were counted. Based on the counts, the patients were divided into two groups: Group A had mast cell counts of > 20/microscopic field; Group B, < 20. TNM staging and histological findings were recorded for both groups. Phenotypes of mast cells were determined using enzymehistochemistry. Total count numbers, the histological differentiation of adenocarcinomas, and phenotypes were evaluated with regard to patient survival rates., Results: Group A had a 5-year survival rate of 45.85%, as compared with Group B's rate of 16.32% (P < 0.01). Group A also represented a higher percentage of well-differentiated adenocarcinomas. In both cancerous tissue and normal lung tissue, the predominant mast cell phenotype was MC(T)., Conclusions: There appears to be a direct relationship between the number of mast cells and clinical outcome in patients with pulmonary adenocarcinoma, even though the mast cells exhibited no significant phenotypic changes.

For an inoperative critical airway obstruction (bilateral bronchial stenoses) from a carcinomatous carina due to the mediastinal lymphnodal metastasis from uterine cancer, we succeeded in improving the patient's severe dyspnea by the combination of bilateral bronchial stent dilatation and a percutaneous cardiopulmonary support (PCPS) system. The imminent airway stenosis with severe dyspnea may have a high risk of asphyxia and contact-flooding during implanting of the stent. By the novel use of PCPS in advance for blood-oxygenation as a respiratory support, we could safely perform the interventional therapy of bronchial expandable metallic stents, and the patient obtained a good quality of life without dyspnea until she died of systemic metastatic cachexia. This technique may possibly be approved as an option for temporary remission therapy of a critical airway obstruction.

The nm23-H1 gene product has been considered as an anti-metastatic protein and the level of its expression has been reported to correlate inversely with metastatic potential in some cancers. However, the expression of nm23-H1 gene product in the metastatic sites have not been studied in detail. We examined the expression of nm23-H1 gene product in surgically resected 46 pairs of primary lung cancers and metastatic lymph nodes by immunohistochemistry. The positive staining of nm23-H1 gene product in primary cancers and metastatic lymph nodes were observed in 56.5 and 67.4%, respectively. The heterogeneity of nm23-H1 gene product expression between primary cancers and metastatic lymph nodes was observed in 41.3%. No correlations were found between the nm23-H1 gene product expression in lung cancers and the patients survival. No significant association was also observed between nm23-H1 gene product expression in lymph nodes and the patients survival. There was, furthermore, no correlation between the heterogeneity of nm23-H1 gene product expression and the patients survival. In conclusion, the level of nm23-H1 gene product expression does not significantly reveal prognostic value in node-positive lung cancers. Expression of nm23-H1 gene product in metastatic lymph nodes was also unrelated to patients survival.

The study population consisted of 42 patients with squamous cell carcinoma and 46 patients with adenocarcinoma of stage I, 12 patients with squamous cell carcinoma and 7 patients with adenocarcinoma of stage II lung cancer who underwent curative surgical resection. Local recurrence and metastasis was not significant in both histological types in stage I, II. Lung and bone metastasis was dominant in the both cases of squamous cell carcinoma, adenocarcinoma and brain metastasis in the cases of adenocarcinoma. Concerning the period to first recurrence following the operation, the recurrences of stage I squamous cell carcinoma occurred 28% within 1 year after surgery, 28% during 1-2 years after surgery and those of stage II squamous cell carcinoma occurred 11% within 1 year. On the other hand, the recurrences of stage I adenocarcinoma occurred 25% within 1 year, 31% during 1-2 years, 25% over 2 years after surgery and those of stage II adenocarcinoma occurred 13% within 1 year. In the cases with squamous cell carcinoma, the 5-year survival rate (56%) of stage I was not significant compared with those (59%) of stage II. On the other hand, in the adenocarcinoma, the 5-year survival rate (54%) of stage I was significantly better than those (29%) of stage II (p less than 0.05).