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Paraneoplastic cerebellar degeneration (PCD) is a paraneoplastic neurological syndrome that is rarely accompanied by seropositivity with a combination of multiple antibodies. We herein report a 50-year-old man with PCD accompanied by small-cell lung cancer (SCLC). This patient was seropositive for anti-glutamic acid decarboxylase 65, anti-SRY-related HMG-box gene 1 and anti-voltage-gated calcium channel antibodies. After chemoradiation therapy without immunotherapy, cerebellar ataxia of the trunk and limbs markedly improved, along with a notable amelioration of SCLC. This case suggests that tumor therapy should be started immediately and that a panel of anti-neuronal antibodies should be evaluated when PCD with SCLC is suspected.

Objectives: The lung was recently re-discovered as a hematopoietic organ for platelet production in mice. However, evidence for the role of the lung in thrombopoiesis in humans is still limited. In this study, we examined megakaryocytes in the pulmonary and systemic circulation, specifically in pulmonary arterial blood (PAB), venous blood (PVB) and peripheral blood using a newly developed microfluidic platform for rare cell isolation., Materials and Methods: We analyzed 23 lung cancer patients who underwent surgery in our institute. PAB and PVB were obtained from the resected lung immediately after surgery. Blood samples were size-selected using a filtration-based microfluidic device and enriched rare cells on glass slide specimens were stained with Papanicolaou (Pap), immunocytochemistry (ICC), and immunofluorescence (IF). Lung tissues were also analyzed by immunohistochemistry., Results: Pap/ICC/IF showed the presence of abundant CD61+/cytokeratin- giant cells with a megakaryocyte lineage in PAB, but only a few in PVB. These megakaryocytes were found to consist of CD61+/CD41+ immature megakaryocytes and CD61+/CD41- mature megakaryocytes with the potential to produce platelets. These findings were confirmed by the conventional hematological analysis of blood smears stained with Giemsa. In analysis of lung cancer, CD61+ megakaryocytes were observed exclusively in the capillaries of non-cancerous tissue, whereas platelets were selectively observed in the tumor blood vessels of cancerous tissue., Conclusions: These results indicate that numerous megakaryocytes migrate from systemic bone marrows to accumulate in PAs and arrest of mature megakaryocytes in the capillaries of normal lung, suggesting the possibility that the lung plays a physiological role in the systemic thrombopoiesis in lung cancer patients., (Copyright © 2018 Elsevier B.V. All rights reserved.)

A 36-year-old woman with a left lung tumor was referred to our hospital since a pathological diagnosis had not been obtained at a previous medical institution. We carried out CT-guided percutaneous lung biopsy with an 18-gauge needle and obtained four samples. Immunological staining revealed the specimens to be CD30- and PAX5-positive, with large dysplastic lymphocytes negative for Bob-1 and Oct-2 with a background of small lymphocytes and eosinophils. Primary pulmonary Hodgkin lymphoma (PPHL) was diagnosed. Although PPHL is very rare, it should be included in the differential diagnosis of lung tumors and immunological staining with CD15 and CD30 is recommended. Furthermore, carefully planned CT-guided lung biopsy is useful for diagnosing PPHL.

We compared claudin-4 with Ber-EP4 and carcinoembryonic antigen as markers to distinguish mesothelioma from lung adenocarcinoma, poorly differentiated lung squamous cell carcinoma, and serous adenocarcinoma of the uterus or ovary. All mesothelioma specimens were negative for claudin-4, but 3 of 18 specimens were focally positive for Ber-EP4. In contrast, lung adenocarcinoma including poorly differentiated adenocarcinoma was highly positive for claudin-4, but expression of Ber-EP4 and carcinoembryonic antigen varied widely. Claudin-4 in poorly differentiated squamous cell carcinoma had a lower positive expression rate than in adenocarcinoma. Granular claudin-4 immunoreactivity was conspicuous in poorly differentiated squamous cell carcinoma; this immunoreactive pattern was also observed in mesothelioma. Claudin-4 was thus considered very useful marker for distinguishing mesothelioma and adenocarcinoma, even if histological specimens are small, as in biopsies that contain limited numbers of tumor cells. However, it should be mentioned that claudin-4 has a limit in discrimination between squamous cell carcinoma from mesothelioma.

This report presents the case of a late relapse of an ovarian granulosa cell tumor (GCT) that metastasized to the lung 36 years after the initial diagnosis. A 72-year-old female demonstrated multiple nodules with extrapleural signs on chest computed tomography. Positron emission tomography with (18)F-fluorodeoxyglucose ([(18)F]FDG-PET) showed that the nodules had no FDG avidity. The nodules, which appeared as polypoid lesions of the visceral pleura on thoracoscopy, were resected and diagnosed as pulmonary metastases from the GCT. This case report indicates that thorough thoracoscopic exploration of the pleural cavity is essential when intrathoracic nodules are seen on postoperative imaging examinations in GCT patients, even when the [(18)F]FDG-PET results are negative.

Background: We investigated whether fluorescent agents, especially vitamin B2, can act as tracers for intraoperative pulmonary sentinel node mapping., Materials and Methods: Vitamin B2, fluorescent beads, and green fluorescent protein (GFP) were each injected into pulmonary parenchyma in 4 pigs (experiment 1). The safety of each tracer was also verified in 12 rats (experiment 2)., Results: Experiment 1: In all groups, the sentinel lymph node was identified in 3 out of the 4 pigs (75%). Speed of agent dispersion: vitamin B2>GFP >fluorescent beads. Level of fluorescence judged as: vitamin B2>GFP=fluorescent beads. Experiment 2: In all groups, all rats survived until sacrifice without complications. In the fluorescent beads group, the fluorescent beads remained in the blood vessels., Conclusion: Vitamin B2 is inexpensive, safe and easy to apply. It is anticipated that clinical application of vitamin B2 for intraoperative pulmonary sentinel node mapping will become possible.

A 2-year 9-month-old girl with a large mass in the right chest underwent middle and inferior lobectomy, after which the mass was pathologically diagnosed as a pleuropulmonary blastoma (PPB). The clinical, radiographic, and pathologic findings were typical. Three courses of postoperative chemotherapy with 2 different regimens were ineffective in preventing multiple metastases of the lung. We then instituted a protocol with irinotecan (CPT-11) and vincristine. After the third course of this protocol the metastases disappeared and there were no recurrences. PPB is a rare pediatric malignant tumor, and no adequate therapy has been defined. This is the only case reported to have been treated with vincristine/irinotecan therapy for the treatment of PPB.

There are still difficulties in determining the risk of recurrence to decide whether to perform selective adjuvant treatment for stage I non-small cell lung cancer. This study reviewed 122 stage I patients who underwent curative surgery to assess the usefulness of an angiogenesis-associated factor as a predictor of recurrence. By immunohistochemical examination, we collected information about tumor-induced vascular endothelial growth factor (VEGF)-A and -C expression at the primary site. During the median follow-up period of 120 months, the overall 10-year survival rate was 53.5%. The 10-year survival rates according to VEGF-A/C expression were as follows: VEGF-A high/VEGF-C high group, 26.0%; VEGF-A high/VEGF-C low group, 42.7%; VEGF-A low/VEGF-C high group, 73.1%; VEGF-A low/VEGF-C low group, 65.1%. The VEGF-A high/VEGF-C high group showed the worst outcome. The diagnostic values of the marker combination for predicting recurrence were as follows: sensitivity, 71.4%; specificity, 63.8%; and accuracy, 65.6%. When stratified by T factor, preferable high values for both negative predictive value and specificity were obtained in patients with stage IA disease. In order to select the patients eligible for selective adjuvant therapy at early stages, especially in stage IA disease, simultaneous assessment of tumor-induced VEGF-A/C warrants further study.

Clear cell carcinoma of the endometrium is a very rare and highly malignant neoplasm that accounts for less than 5% of endometrial carcinoma. Survival of patients in the advanced stage is poor, and the treatment of choice is not clear. We report the case of a 62-year-old woman who had Stage IVb advanced clear cell carcinoma of the endometrium with multiple lung metastases. The lesions were considered surgically incurable, so she was placed on neoadjuvant chemotherapy of combination carboplatin (CBDCA) (AUC 5, day 1) plus weekly paclitaxel (PTX) (70 mg/m(2), day 1, 8, 15). After 3 courses of chemotherapy, the uterine tumor was obviously reduced, and lung metastases had disappeared. Therefore, she underwent the operation. The current case suggests that combination CBDCA plus weekly PTX is effective against advanced clear cell carcinoma of the endometrium.

Long-term control of malignant pleural effusion is an important goal of therapy in patients with pleural dissemination. The authors have carried out limited operations combined with parietal pleurectomy (PL) for non-small cell lung cancer patients with pleural dissemination, based on the hypothesis that the most effective target area for controlling malignant pleural effusion is the parietal pleura. In our 25 years of experience, 54 patients with pleural dissemination (26 also had malignant pleural effusion) have undergone this surgical treatment. The operative procedures used for resection of lung parenchyma were partial resection in 25 patients, lobectomy in 24, bilobectomy in two, segmentectomy in two, and no parenchymal resection (PL only) in one. Postoperative intrapleural chemotherapy and systemic chemotherapy (2-4 cycles) also were applied in 43 patients. The pathological stages were IIIB in 44 patients and IV in ten. The overall three-, five-, and ten-year survival rates were 29.0%, 15.0%, and 7.5%, respectively. Twenty patients survived for more than two years. Recurrent malignant pleural effusion developed in only two of 30 patients whose recurrent patterns could be clearly identified. Although this was not a clinical randomized comparative study, multimodality treatment that included the use of PL appears to be a useful option for treatment of this disease in appropriately selected patients.

Thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD) are critical enzymes in nucleic acid metabolism. Proliferating cell nuclear antigen (PCNA) is a specific protein that is correlated with proliferative activity of cells. The TS gene has a variable number of tandem repeats (VNTR) in its 5'-untranslated region and a single nucleotide polymorphism (SNP) in the VNTR area. We examined the association of in vitro sensitivity to anticancer drugs with TS polymorphism, TS, DPD, and PCNA mRNA expression using human lung cancer tissues. Seventy-eight surgically resected lung cancer tissues were tested for in vitro sensitivity to 5-fluorouracil, cisplatin (CDDP), carboplatin (CBDCA), irinotecan, docetaxel, and gemcitabine by histoculture and MTT assay. The TS polymorphisms were analyzed by PCR and PCR-RFLP. TS, DPD, and PCNA mRNA expression levels were quantified by real-time RT-PCR and normalized relative to beta-actin mRNA expression. The inhibition rates (IRs) of CDDP and CBDCA were significantly correlated with TS/PCNA, the ratio of TS/actin and PCNA/actin, and DPD/PCNA, the ratio of DPD/actin and PCNA/actin. This correlation was further explored by subgroup analyses according to TS VNTR or TS functional type, in which 2R/3G, 3C/3G, or 3G/3G were classified into H-type group and 2R/2R, 2R/3C, or 3C/3C into L-type group. The associations of TS/PCNA and DPD/PCNA with the IRs of CDDP, CBDCA remained significant in the 3R/3R group and H-type group. These results suggest that in vitro sensitivity to platinum-derived drugs, CDDP and CBDCA, is associated with PCNA-normalized mRNA expression of TS and DPD in human lung cancer tissues, as affected by the TS polymorphism. The clinical significance of these pharmacogenomic markers for chemotherapy regimens with platinum-derived drugs should be investigated further for personalized treatment of lung cancer.

The purpose of this study was to evaluate the clinical characteristics and results of lung cancer patients with carcinomatous pleuritis on initial relapse. Over the past decade, seven patients out of 595 surgically treated lung cancer patients developed carcinomatous pleuritis as the initial sign of relapse. All patients had undergone complete resection of the primary peripheral type adenocarcinoma. Only 3 cases showed obvious visceral pleural invasion, while venous or lymphatic invasion were frequently found in the histological sections. The mean disease-free interval after surgery was 30.9 months. The median survival after the development of carcinomatous pleuritis was 14 months. The results showed the possible association of blood/lymphatic routes with the development of this type of recurrence. In some lung cancer patients with carcinomatous pleuritis on initial relapse, long-term survival can be expected by aggressive interventions consisting of intrathoracic and/or systemic chemotherapies.

Background: We evaluated the pathologic and biological aspects of lung tumors 3.0 cm or less in diameter with the appearance of ground-glass opacity (GGO)., Methods: Of 988 patients with non-small cell lung cancer who underwent operations at our institute between January 1994 and December 2004, 87 resected lung tumor specimens that showed GGO appearance on helical computed tomography were obtained from 81 patients. Forty-four lesions were pure GGO with no solid component in the tumor and 43 lesions were mixed GGO consisting of areas of attenuation with a solid component. Together with histological features, MIB1 and nm23 expression within tumors were examined immunohistochemically., Results: The mean tumor size in the pure GGO group was significantly smaller than that in the mixed GGO group. The composition of pathologic subtypes and biological characteristics were clearly different between the two groups. Although atypical adenomatous hyperplasia and localized bronchioloalveolar cell carcinoma of Noguchi's A and B were the predominant pathologic subtypes and nm23 negativity was rare in the pure GGO group, a high score for expression of MIB1 was often found in pure GGO tumors even though the tumors were less than 10 mm in diameter., Conclusions: If the tumor is 2 cm or less in diameter, the ability of invasion and metastasis seems to be low in pure GGO tumors. However, the proliferation ability of these tumors suggests the necessity of a careful follow-up schedule if the tumor is greater than 5 mm in diameter. For mixed GGO tumors, surgical resection instead of observation is justified.

For successful intrapleural chemotherapy, intrapleural drug activity should be maintained for as long as possible. This interim report presents the results of treatment with paclitaxel administered by 24-hour intrathoracic infusion as an adjunct to selective surgical management and/or systemic chemotherapy for controlling malignant pleural effusion. Thirteen patients with carcinomatous pleuritis were enrolled in the study between October 2001 and September 2004. The sites of primary disease were the lung in 12 patients and the breast in one patient. Paclitaxel (120 mg/m2) was administered by 24-hour intrathoracic infusion. Seven patients underwent elective surgical treatment and 11 patients received adjuvant systemic chemotherapy. Mild toxicity occurred in 7 cases, and chest pain and neutropenia were dominant. During a median follow-up period of 9 months (range, 2-33 months), malignant effusion was controlled successfully in 11 patients (84.6%). The multimodality treatment, including the use of paclitaxel, in this manner merits further investigation for possible intervention for malignant pleural effusion originating in lung and breast neoplasms.

Background: There is still debate regarding the use of surgery in the management of non-small cell lung cancer patients with N2 disease. The primary aim of the present study was analysis of the results of initial operations in non-small cell lung cancer patients with single-level N2 disease., Methods: Ninety-four patients with the disease who underwent initial surgery consisting of complete resection of the primary site plus systematic lymphadenectomy were examined. We also immunohistochemically examined lymphatic vessel density and vascular endothelial growth factor-C expression., Results: The overall 5- and 10-year survival rates for the 94 patients were 27.1% and 12.1%, respectively, with a median survival of 22 months. When stratified by skipping status, the 5-year survival rates for the patients in skip-N2 and non-skip-N2 groups were 33.4% and 19.8%, respectively (p = 0.0189). Skip metastasis, T factor, subcarinal lymph node metastasis, and adjuvant chemotherapy were recognized as independent prognostic indicators. In both skip-N2 and non-skip-N2 groups, distant relapse was the dominant pattern of recurrence. Although the peritumoral lymphatic vessel density was associated with vascular endothelial growth factor-C expression in tumors, the lymphangiogenic profile appeared to be different between skip-N2 and non-skip-N2 tumors, suggesting different nodal metastatic process., Conclusions: Lung cancer patients with single-level N2 disease are an oncologically heterogeneous cohort. Although further studies involving randomized comparisons are required, the poor outcomes found here indicate that the initial operation has yet to be validated for patients with this disease.

The anatomical abnormalities of the pulmonary veins may have a serious impact on complications that may arise during pulmonary lobectomy. We present a surgical case of left lung cancer in a patient, who was a 69-year-old male, with the left superior and inferior pulmonary veins forming a common trunk outside the pericardium. In this present case, because of extensive adhesions, incomplete lobulation, and tumor infiltration of the main pulmonary artery, we could not identity the common trunk with certainty before excising the left upper lobe. Although this patient was fortunately discharged without complications, there was no choice but to perform pneumonectomy because of the interruption of the inferior pulmonary vein. Retrospectively, the preoperative CT films showed the anatomical anomalies involving the pulmonary veins. However, since the length of the common trunk outside the pericardium was short and the inferior pulmonary vein was thinner than usual and its venous distribution conformed to a normal structure, the anatomy appeared normal. In excising the pulmonary lobe, it is mandatory to ascertain the distribution of the vascular system prior to surgery.

This retrospective analysis was undertaken to review our results of treatment of lung cancers with invasion of non-apical and non-vertebral chest wall structures. In summary of our experience, although relatively good prognosis can be expected in N0M0 patients with the histological type of adenocarcinoma by initial operation, distant relapse remains a major problem of the disease. Furthermore, our results are in agreement with the idea that postoperative adjuvant therapy is of little value in patients with complete resection. To ameliorate surgical outcomes, induction treatment should be considered and preoperative staging assessment needs to be strictly done for proper selection of patients with this locally advanced disease. The indication of initial operation needs to be cautiously determined for patients with this disease.

Background and Objectives: The long-term control of malignant effusion is necessary to achieve long-term survival in lung cancer patients with carcinomatous pleuritis. This report describes our results of limited operations including parietal pleurectomy (pl) on a hypothesis that the most effective target area for controlling malignant pleural effusion is the parietal pleura., Methods: Forty-two patients with pleural dissemination with/without malignant pleural effusion were analyzed retrospectively. The operative procedures used were partial resection of the primary site with pl in 20 cases, segmentectomy with pl in 2 cases, lobectomy with pl in 19 cases, and pl only in 1 case. Postoperative adjuvant treatment was performed in 31 patients., Results: Adenocarcinoma was the dominant histology, and the pathological stages were IIIB in 34 cases and IV (intrapulmonary metastasis) in 8 cases. The overall 3-, 5-, and 10-year survival rates were 30.1%, 17.2%, and 10.3%, respectively. When stratified by the TNM classification, the overall 3-, 5-, and 10-year survival rates were 56.3%, 32.1%, and 24.1%, respectively, in the T4N0M0 group and 21.1%, 7.0%, and 0%, respectively, in the T4N1-2M0 group (P = 0.0257). Among the 24 patients whose recurrent patterns could be identified, only 2 patients developed recurrent malignant effusion., Conclusions: With appropriate patient selection, the use of limited surgery combined with pl followed by intrapleural and systemic chemotherapy appears to be effective in management of the disease., (Copyright 2005 Wiley-Liss, Inc.)

Objective: The aim of this study was to evaluate the expression of dysadherin and E-cadherin and to investigate their clinical significance as prognostic factors in non-small cell lung cancer., Methods: Non-small cell lung cancer specimens were obtained from 131 patients undergoing clinically indicated operations at the Department of General and Cardiothoracic Surgery, Kanazawa University Hospital, between 1995 and 1997. All patients had undergone curative resection of the primary tumor, including systematic lymph node dissection. The avidin-biotin-peroxidase complex method was used for immunostaining of dysadherin and E-cadherin., Results: Among the 131 lung cancer specimens, 46 (35.1%) tumors were positively stained with dysadherin. Preserved membranous E-cadherin staining was present in 45.8% (60/131) of cases. In this analysis dysadherin expression was not correlated with E-cadherin expression (P = .1333), but a significant association was observed between dysadherin expression and survival time. The overall survival of patients with dysadherin-positive tumors was significantly worse than that of those with dysadherin-negative tumors (P = .0059). Patients with reduced E-cadherin immunopositivity survived significantly shorter than those with preserved E-cadherin immunopositivity (P = .0406). The overall survival of patients with positive dysadherin and reduced E-cadherin expression was significantly worse than that of patients with negative dysadherin and preserved E-cadherin expression (P = .0002). Multivariate analysis revealed the independent prognostic value of dysadherin positivity, reduced E-cadherin expression, and lymph node metastasis on overall survival., Conclusions: Dysadherin expression is an independent prognostic factor of survival in patients with non-small cell lung cancer, and combined immunohistochemical analysis of dysadherin and E-cadherin expression might provide further prognostic information.

We evaluated the efficacy of perioperative targeting brachytherapy for lung cancer invading the chest wall. Between 1998 and 2003, 7 patients underwent perioperative targeting brachytherapy for lung cancer invading the chest wall. There were 5 male and 2 female patients. The mean age was 63.3 years, with a range of 45 to 77 years. All patients underwent complete resection including the chest wall combined resection. During the operation, plastic afterloading catheters fixed on the Vicryl mesh at interval of 1 cm were placed on the site of chest wall resection. From the third to sixth day after the operation, 15 to 32 Gy of radiation was delivered over 3 or 4 days using a high dose rate remote afterloading system. The area targeted for brachytherapy was determined by a computed tomography (CT) scanner translator with a computer program for radiation planning. The median postoperative hospital stay was 35 days. Local recurrences were observed in 2 patients, but there was no evidence of recurrence in the margin of the resected chest wall. We believe that this short period of treatment and the low side effects enhances the quality of the patients. Prevention of local recurrence was achieved in short term follow-up.

Background: The aim of the present study was to evaluate the diagnostic utility of levels of circulating vascular endothelial growth factor (VEGF)-C, matrix metalloproteinase-9 (MMP-9), and VEGF and to verify that the combination assay of these circulating factors is a clinically useful indicator to predict the presence of lymph node metastasis in non-small cell lung cancer (NSCLC)., Methods: A series of 78 patients who underwent surgery for NSCLC was used in this study. Serum VEGF-C and VEGF and plasma MMP-9 levels were analyzed with enzyme-linked immunosorbent assay (ELISA) kits. Logistic regression models were used to analyze the influence of VEGF-C, MMP, and VEGF levels on the probability of presence or absence of lymph node metastasis., Results: Patients with lymph node metastasis had higher serum VEGF- C, VEGF, and plasma MMP-9 concentrations than did those without metastasis (VEGF-C, P = .0004; VEGF, P = .001). Serum VEGF- C reached a sensitivity of 85% and specificity of 68% when a cutoff value of 1762.0 pg/mL was applied, while VEGF reached 80% sensitivity and 59% specificity at 316.8 pg/mL. MMP-9 reached a sensitivity of 63% and specificity of 75% when a cutoff value of 51.4 ng/mL was applied. In the ROC curve analysis, VEGF-C (0.761) had the biggest areas under the ROC curve, followed by MMP-9 (0.723) and VEGF (0.694). Combination assay of three markers had higher sensitivity and specificity for prediction than single-marker assays (AUC = 0.837)., Conclusions: This study has confirmed that combination assay of three markers to determine VEGF-C, MMP-9, and VEGF expression in circulation detects lymph node metastasis in NSCLC with higher accuracy than single-marker assays.

Aims: This study reviews our 30 years experience in the clinical assessment and surgical management of bilateral multiple primary lung cancer (BMPLC)., Methods: Between January 1973 and December 2001, 1906 patients with primary lung cancer underwent surgical resection in Kanazawa University Hospital. Thirty-seven patients (1.9%) who had developed a BMPLC using the criteria of Martini and Antakli., Results: Eighteen patients had synchronous lesions, and 18 patients had metachronous lesions. One patient had synchronous and metachronous lesions. Overall 10-year survival was 56%. The actuarial 5-year survival for bilateral synchronous cancers was 69%, median survival (MST) 90 months (range 8-153 months), and 10-year survival was 47%. The actuarial 5-year survival for second metachronous cancers was 51%, with an MST of 114 months (range 6-192 months)., Conclusion: Aggressive surgical therapy is effective in patients with a bilateral MPLC if they satisfy the usual criteria of operability. The surgical methods that preserve healthy lung tissue such as sleeve resection and limited resection must be selected in compliance with cancer characters.

Study Objective: Accurate tumor staging is essential for choosing the appropriate treatment strategy for lung cancer. CT of the chest is the most commonly used noninvasive staging method of the lymph node metastasis, but it is far from satisfying. We evaluated whether circulating vascular endothelial growth factor (VEGF)-C could give additional information for diagnosing lymph node metastasis in patients with lung cancer., Patients and Method: Serum samples were obtained from 116 patients with primary non-small cell lung cancer (NSCLC). All patients underwent preoperative CT of the thorax. Clinical T and N stages were compared to the final T and N stages obtained from pathologic findings. Serum VEGF-C concentration was assayed by commercially available sandwich enzyme-linked immunosorbent assay. We evaluated the utility of serum VEGF-C level as a marker for nodal metastasis comparing the utility of CT., Results: Preoperative and final T categories completely agreed in 82.8%. Regarding nodal metastasis, the accuracy of CT was 68.1%. Patients with lymph node metastasis showed higher serum VEGF-C concentrations than those without lymph node metastasis (p = 0.0007). Serum VEGF-C reached the highest sensitivity and specificity in diagnosing lymph node metastasis when a cut-off value of 1,850.6 pg/mL was applied (sensitivity, 70.0%; specificity, 77.3%). Serum VEGF-C visually correlated with CT scan in the detection of lymph node metastasis (sensitivity, 74.0%; specificity, 80.3%; positive predictive value, 74.0%; negative predictive value, 80.3%; accuracy, 77.6%). When the cases were limited to adenocarcinoma, better results could be obtained., Conclusions: Serum VEGF-C is a reliable marker for lymph node metastasis in NSCLC. Serum VEGF-C evaluation and CT examination are complementary to each other for accurate lymph node staging in NSCLC.

We present a case of a 65-year-old woman whose thyroid cancer metastasized to the lesion of primary lung cancer. Ten years after total thyroidectomy for thyroid cancer, chest radiograph by medical check-up demonstrated three nodular lesions in the bilateral lung fields. Segmental resection of the left S6, partial resection of right S4 and left S10 were performed to remove those lesions. Histologically, small nodules in the right S4 and S10 were diagnosed as a metastatic tumor of thyroid and well differentiated adenocarcinoma, respectively. Left S6 lesion 1.5 cm in diameter was also diagnosed as well-differentiated adenocarcinoma (Noguchi type C), however, small metastatic foci of papillary adenocarcinoma was identified within the lesion which revealed to be "cancer in cancer metastasis". Metastasis of cancer to another primary cancer is a rare event. We discuss interesting phenomenon of cancer in cancer metastasis with a review of the literature.

Background: The authors measured circulating vascular endothelial growth factor-C (VEGF-C) and vascular endothelial growth factor (VEGF) levels in patients with primary nonsmall cell lung carcinoma and assessed its usefulness as a diagnostic tool for determining lymph node metastasis., Methods: Ninety-two patients with nonsmall cell lung carcinoma and 58 patients with benign tumors of the lung were included in the current study, as well as 42 healthy control patients. Circulating VEGF-C and VEGF levels were assessed by enzyme-linked immunosorbent assay., Results: Serum VEGF-C concentration was higher in patients with lung carcinoma than in patients with benign tumors or in healthy control patients. Patients with lymph node metastasis revealed higher serum VEGF-C and VEGF concentrations than those without. The median level of VEGF-C and VEGF according to lymphatic vessel invasion and venous invasion was higher in the group with invasion than in the group without. These differences were most significant among patients with VEGF-C with lymphatic vessel invasion (P = 0.0066 vs. P = 0.026) and in patients with VEGF with venous invasion (P = 0.19 vs. P = 0.011). Serum VEGF-C levels reached a sensitivity of 79% and a specificity of 72% with a cutoff value of 1756.0 pg/mL, whereas VEGF levels reached 68% sensitivity and 70% specificity at 327.8 pg/mL. If 92 patients were divided into 4 groups according to the combination of VEGF-C and VEGF levels, the positive predictive value was 84.2%, the negative predictive value was 95.8%, and accuracy was 93.1%., Conclusions: Circulating VEGF-C levels may provide additional information for distinguishing between the absence and presence of lymph node metastasis in patients with lung carcinoma., (Copyright 2003 American Cancer Society.DOI 10.1002/cncr.11529)

A 67-year-old man was referred to our hospital because of positive sputum cytology. Despite detailed examination, the malignant cell source remained elusive. Twenty months later, CT revealed two nodules in the right S1 and S10 regions which were resected. A year following the operation, gastoendoscopy showed a stomach tumor. Total gastrectomy with lymph node dissection was performed. Histologically, this patient was diagnosed with double primary lung cancer with metastasis to the stomach. The tumors of the lung, stomach and tumor cells in the sputum showed the same immunoreactivities of autocrine motility factor receptor (AMFR). In our institution, of 38 occult lung cancers encountered during the past 10 years, four (10.5%) occurred in the peripheral region. The presented four cases of radiologically occult lung cancer in the peripheral resion revealed bad prognosis, as three out of four patients were dead within 24 months after surgery. All of the four cases showed venous invasion, though the size of the primary tumor was small. Careful follow-up, including monitoring for distant metastasis, is necessary in radiologically occult peripheral lung cancer.

Objective: The diagnosis of small-sized (2 cm or less) non-small cell lung cancer (NSCLC) has increased with the development of computed tomography (CT), whereas unexpected extensive multiple-level mediastinal involvement has been occasionally detected in this small-sized lung cancer. To establish the optimal surgical strategy, we retrospectively analyzed the clinicopathologic features, efficacy of preoperative investigations and lobe specific patterns of nodal spread in small-sized NSCLC with mediastinal involvement., Methods: Among 1,550 resected lung cancer cases between 1981 and 2000, 267 (17.2%) had peripheral small-sized NSCLC. Of these, 29 patients (10.8%) with mediastinal lymph node involvement who underwent pulmonary resection and systematic nodal dissection were reviewed., Results: Among 29 patients, 27 patients (93.1%) were adenocarcinoma, and 51.7% (15/29) showed no lymph node enlargement on CT (cN0). Surgical pathology revealed multiple-level mediastinal involvement in 65.5% (19/29) of all patients and 60.0% (9/15) of cN0 patients. All of right upper lobe tumors (n=11) showed multiple-level involvement. Thallium-201 single photon emission computed tomography (201Tl-SPECT) was positive for increased focal uptake in the mediastinum in 72.7% (8/11) of patients., Conclusions: The vast majority of cases were adenocarcinoma, and two thirds of them showed multiple-level mediastinal involvement, even in cN0 patients. We thus recommend to perform systematic nodal dissection or meticulous sampling for accurate intrathoracic staging, especially for right upper lobe tumor. 201Tl-SPECT appears to be more sensitive preoperative investigation for mediastinal metastasis compared with CT scan.

We assessed the diagnostic value of circulating VEGF as a tumor marker in patients with lung cancer and compared its clinical utility with that of other markers such as carcinoembryonic antigen (CEA) and cytokeratin 19 (CYFRA). One hundred and sixty non-small cell lung cancer patients and 70 healthy volunteers were included in the study. Circulating VEGF was assessed by enzyme-linked immunosorbent assay (ELISA). The serum concentrations of both CEA and CYFRA were measured by means of immunoradiometric assays. The diagnostic value of plasma VEGF (VEGFp) was better than that of CYFRA and similar to that of CEA. When the diagnostic value of VEGFp and CEA for the diagnosis of adenocarcinoma was compared, the two markers proved to have nearly equal discriminatory power. In diagnosing squamous cell carcinoma, VEGFp showed less discrimination than CYFRA. When the diagnostic value of VEGFp was analyzed for stage I adenocarcinoma patients, VEGFp was slightly more discriminatory than CEA. The combination assay of VEGFp and CEA had a sensitivity of 75% and a specificity of 60% at a cutoff of 104.4 pg/mL for VEGFp and 5.2 ng/mL for CEA. The combination of VEGF and CEA was superior to CEA alone in the early diagnosis of adenocarcinoma of the lung.

The results of radiosurgery for treatment of patients with non-small-cell lung cancer with brain metastasis as the initial relapse were evaluated. Twenty-three patients were included in the study. The dominant pathologic type was adenocarcinoma (56.5%). In the mean interval of 13.7 months (range, 3-52 months) between the lung operation and treatment of brain metastasis, a solitary lesion developed in 9 patients and multiple lesions developed in 14 patients. The modalities used for brain metastasis were gamma-knife radiation therapy (GKS) in nine patients, GKS plus operation in six, GKS plus whole brain radiation therapy (WBR) in two, operation plus WBR in two, operation only in one, WBR only in two, and no treatment in one. The 1- and 3-year survival rates after treatment of brain were 47.3% and 7.4%, respectively. The prognostic impact of stage and number of brain metastases was not clear. Primary tumor size and adjuvant chemotherapy after the lung operation significantly affected survival after the management of brain metastasis. The low invasive radiosurgery is beneficial in terms of improving the quality of life of patients.

Study Objective: We evaluated the expression of vascular endothelial growth factor (VEGF) in airways in patients with lung cancer., Methods: BAL fluid (BALF) and plasma samples were obtained from 41 patients with primary lung carcinomas and 7 patients with noncancerous diseases, and were analyzed for VEGF by an enzyme-linked immunosorbent assay. After standardization with the albumin protein levels, the relative intensity (VEGF index) was determined as the ratio of VEGF expression on the disease side to that on the healthy side., Results: In all cases, VEGF concentrations in BALF were greater than those in plasma samples. On the healthy side, the mean value of VEGF in BALF was significantly greater in lung cancer patients than in patients with noncancerous diseases (p = 0.0470). While age, gender, location of cancer (right vs left), histology (adenocarcinoma vs squamous cell carcinoma), and T factor (T1/2 vs T3/4) did not affect the VEGF levels in BALF, the VEGF index was inversely associated with distant metastasis and nodal involvement. The VEGF index of patients in stage I was significantly greater than that of patients in stage IV (p = 0.0308)., Conclusions: The VEGF expression in airways is likely to reflect the response to tumor angiogenesis on the host side. Of direct clinical relevance is that the assessment of VEGF concentrations in airways may provide information concerning the dependency of tumor angiogenesis on VEGF, which is variable according to tumor progression.

This report presents a case of lung carcinoid tumor that showed a growth pattern similar to that of a superior sulcus tumor (SST). A 63-year-old man was referred to our hospital and was diagnosed to have a stage IV (T3N2M1) SST on his right side. After three cycles of induction therapy with MVP (methotrexate/vinblastine/prednisolone) and a total dose of 45 Gy radiation given to the chest lesion, the clinical stage was restaged down to IIB (T3N0M0). A salvage operation was performed (upper lobectomy plus chest wall combined resection including the first to fourth ribs) followed by targeting adjuvant brachytherapy. The results of a histologic examination of the resected specimen revealed the tumor to be an atypical carcinoid tumor.

Roentgenographically occult lung cancers (ROLCs) are rare but are usually curable if they are properly diagnosed and treated. Between 1977 and 2000, we treated 51 patients with early hilar lung cancer (as defined by the Japan Lung Cancer Society) of ROLC form. If the occurrence of cancer is confined to segmental bronchi, we preserve the lung tissue as far as possible by using a sleeve segmentectomy. Eight of the 51 patients underwent sleeve segmentectomy. All 8 of these patients were men who were heavy smokers and had a mean age of 64.9 years (range, 59-74 years). The cancerous locations were R-B6 in 4 patients, L-B(1+2+3) in 2 patients, L-B(4+5) in 1 patient, and L-B6 in 1 patient. Two patients had double cancers (synchronous in one case and metachronous in the other). All 8 of the patients had squamous cell carcinoma, 3 of whose lesions were carcinoma in situ. The segments resected were R-S(6) in 3 patients, L-S(1+2+3) in 2 patients, L-S(4+5) in 1 patient, L-S(6) in 1 patient, and R-S6 combined with the middle lobe in 1 patient. There were no cases of morbidity or mortality. However, 1 patient who had undergone a left lower lobectomy for synchronous advanced squamous cell carcinoma 4 months before R-S(6) sleeve segmentectomy for contralateral early hilar lung cancer died of recurrence in the mediastinal lymph nodes 63 months after the first operation. Two patients died of other causes: one of pneumonia 61 months after L-S(4+5) sleeve segmentectomy and the other of myelopathy 36 months after L-S(1+2+3) sleeve segmentectomy. The remaining 5 patients are alive and well 178, 121, 109, 94, and 14 months after surgery. Sleeve segmentectomy is a curative operation for early stage squamous cell carcinoma of the segmental bronchus that preserves pulmonary function and should be used to treat patients carefully selected for the correct indications.

Objective: We retrospectively reviewed nodal status of the patients with peripheral small-sized lung cancer grouped by cell type and tumor size to evaluate the necessity of systematic nodal dissection in this group of patients., Methods: From 1973 to 1998, 1713 patients underwent pulmonary resection for primary lung cancer in Kanazawa University. Among them, 225 patients (13.1%) with peripheral small-sized (2 cm or less) lung cancer underwent lobectomy and systematic nodal dissection were retrospectively reviewed. The maximum diameter of the tumor was measured on formalin-fixed surgical specimens., Results: The histological types were adenocarcinoma in 170 (75.6%), squamous cell carcinoma in 20 (8.9%), small cell carcinoma in 19 (8.4%) and others in 16 (7.1%). Among 170 adenocarcinoma patients, 38 (22.4%) showed hilar or mediastinal lymph node metastases. No mediastinal lymph node metastasis was encountered in all squamous cell carcinoma (n = 20), adenocarcinoma < or = 1 cm (n = 16), small cell carcinoma < or = 1 cm (n = 4), and adenocarcinoma of Noguchi's classification type A or B (n = 24)., Conclusions: Mediastinal nodal dissection would be unnecessary in the patients with peripheral small-sized lung cancer fulfilling these criteria: (1) squamous cell carcinoma < or = 2 cm; (2) adenocarcinoma < or = 1 cm; (3) localized bronchioloalveolar carcinoma < or = 2 cm without foci of active fibroblastic proliferation in histology (Noguchi's classification type A or B adenocarcinoma); (4) small cell carcinoma < or = 1 cm. Candidates fulfilling above criteria were 28.4% (64/225) of small-sized lung cancer and 10.9% of stage IA patients. The establishment of a universally accepted therapeutic strategy for small-sized lung cancer is indispensable in the clinical spread of various sort of limited resections.

Objective: We sought to determine the critical diameter of a peripheral non-small cell lung cancer tumor less than which no evidence of nodal micrometastasis is present., Methods: Samples of 3081 lymph nodes from 181 patients with stage I peripheral lung cancer (155 with adenocarcinoma and 26 with squamous cell carcinoma) who had undergone complete resection with systematic lymphadenectomy were used in the study. In the samples immunohistochemical staining for cytokeratin was performed. The expression of vascular endothelial growth factor (VEGF) at primary sites was also immunohistochemically assessed., Results: Nodal micrometastasis was detected in 44 patients. The mean tumor sizes were 2.2 +/- 1.3 cm (range, 1.0-7.0 cm) in nodal micrometastasis-positive adenocarcinoma, 2.1 +/- 0.9 cm (range, 0.5-6.0 cm) in nodal micrometastasis-negative adenocarcinoma, 4.8 +/- 2.3 cm (range, 2.2-10.0 cm) in nodal micrometastasis-positive squamous cell carcinoma, and 3.2 +/- 2.1 cm (range, 0-9.0 cm) in nodal micrometastasis-negative squamous cell carcinoma. The tumor size in the nodal micrometastasis-positive group tended to be greater than that in the nodal micrometastasis-negative group in squamous cell carcinomas, but there was no significant difference in adenocarcinomas. Nodal micrometastasis was not found in patients with squamous cell carcinoma of 2.0 cm or less in diameter. However, nodal micrometastasis was found in 20% (19/95) of the patients with adenocarcinoma of 1.1 to 2.0 cm in diameter and even in 4 of 11 patients with adenocarcinoma of 1.0 cm or less. Among the patients with nodal micrometastasis, survival of patients with vascular endothelial growth factor overexpression was worse than that of patients without it. The survival of patients with nodal micrometastasis without vascular endothelial growth factor overexpression was comparable with that of patients without nodal micrometastasis., Conclusion: A limited surgical intervention without lymphadenectomy is validated for squamous cell carcinoma of 2.0 cm or less without pleural involvement. In adenocarcinoma the tumor size itself is not a reliable guide for nodal micrometastasis status. In patients with nodal micrometastasis with vascular endothelial growth factor overexpression, the risk of systemic disease should be considered.

We assessed the clinical utility of circulating angiogenic factors as a predictor for tumor angiogenesis in primary lung cancer. Circulating vascular endothelial growth factor (VEGF) and intratumoral VEGF were assessed by enzyme-linked immuno-sorbent assay (ELISA). There was a significant increase in the mean value of both plasma and serum VEGF concentration in primary lung cancer patients (n=97) compared to those of healthy controls (n=59). There was a significant correlation between plasma VEGF levels and microvessel density (MVD), and also between plasma VEGF and intratumoral VEGF levels. Plasma VEGF in patients with lung cancer appears to be a useful indicator of tumor angiogenesis.

Expression of vascular endothelial growth factor (VEGF)-C and that of its receptors were assessed in non-small cell lung cancer. Immunohistochemistry revealed positive VEGF-C expression in 38.7% (24/62) of the patients studied. A significant positive correlation was found between VEGF-C in cancer cells and VEGF receptor-3 (VEGFR-3) in vascular endothelial cells, but not between VEGF-C in cancer cells and VEGFR-2 in endothelial cells. In this cohort of lung cancer patients, VEGF-C expression was significantly associated with lymph node metastasis, lymphatic vessel invasion, and worse outcomes after the operation. Although the independent prognostic impact of VEGF-C and VEGFR-3 was not clear, VEGFR-2 expression in endothelial cells retained the independency as the prognostic indicator. In light of these findings, we conclude that VEGF-C plays an important role in lymphatic invasion/metastasis and tumour progression in non-small cell lung cancer.

Background: Detection of occult micrometastasis in regional lymph nodes is crucial for diagnosis and selection of appropriate therapy for patients with pN0 non-small-cell lung carcinoma. Using immunohistochemical staining, we evaluated the impact of detection of occult micrometastasis on the prevalence and prognosis of patients with lung adenocarcinoma of 2.0 cm or less in diameter., Methods: A total of 103 pN0 disease patients with peripheral lung adenocarcinomas of 2.0 cm or less in diameter were enrolled in this study. We studied 1,438 regional lymph nodes for occult micrometastasis by immunohistochemical staining for cytokeratins., Results: Micrometastasis was detected in 49 lymph nodes (3.4%) of 21 patients (20.4%) but not in patients with localized bronchioloalveolar carcinoma or localized bronchioloalveolar carcinoma with foci of collapse of alveolar structure. The 5-year survival rate (61.9%) of patients with micrometastasis was significantly (p = 0.0041) lower than that of patients without micrometastasis (86.3%)., Conclusions: There still remains a risk of nodal micrometastasis in patients with primary peripheral lung adenocarcinoma, even if the diameter of the tumor is smaller than 2.0 cm. Selection of patients for limited surgery should be done prudently, taking into consideration the risk of nodal micrometastasis.

We assessed the association of vascular endothelial growth factor (VEGF) and nm23 expression with occult micrometastasis in lung cancer. As destination sites for micrometastasis, we scrutinized lymph node (LN) and bone marrow (BM) specimens. For LN, 122 stage I patients who had received curative operations were studied. As regards BM, 203 patients in stage I - IV who underwent operations were registered. Immunohistochemical anti-cytokeratin staining was used to detect microdissemination of cancer cells. The VEGF and the nm23 expression at the primary sites were immunohistochemically studied in 285 cases in total. The percentages of the patients with microdissemination were 28.7% for LN and 42.4% for BM. The outcome for the patients with LN or BM microdissemination was significantly worse than that for patients without it. The increased VEGF and the decreased nm23 expression within primary tumors were significantly associated with LN and BM microdissemination. The results indicate possible value of using these biological markers to predict the risk of systemic micrometastasis in non-small cell lung cancer.

Background: Expression of autocrine motility factor receptor (AMFR) associates with increased cell migration and poor survival in certain types of human cancers. We assessed the possible correlation between AMFR, clinicopathologic features, and survival in stage I non-small cell lung cancer (NSCLC)., Methods: AMFR expression was analyzed immunohistochemically, using a monoclonal antibody (3F3A) in tumor specimens from 97 patients with curative resection. Vascular endothelial growth factor (VEGF) expression was also examined after accounting for AMFR expression., Results: Out of 97 tumors, 38 (39.2%) were positively stained with AMFR. The AMFR expression was significantly associated with histologic type of tumor, mainly in adenocarcinoma. Overall survival of patients with AMFR-positive tumors was significantly worse than that of AMFR-negative tumors (p = 0.0050). The AMFR expression appears to be associated with VEGF expression. Patients who were AMFR positive and had high VEGF expression had a worse prognosis compared with the AMFR-negative and low VEGF-expression group (p < 0.0001). Multivariate analysis revealed an independent prognostic impact of AMFR on survival (p = 0.0039)., Conclusions: These results indicate that evaluation of AMFR expression may provide useful guidance in follow-up of patients with NSCLC.

Curative resection of a second primary lung cancer in a patient who survived small-cell lung cancer is reported. Small-cell cancer had been treated with chemotherapy followed by surgical resection 12 years before. The patient developed squamous cell cancer as the second primary tumor and underwent lobectomy with mediastinal node dissection. Patients who undergo two curative pulmonary resections of both primary and second primary lung cancer are extremely rare. The patient is alive 176 months after the initial diagnosis of small-cell lung cancer and 28 months after resection for his second primary lung cancer. Careful follow-up at an interval of 3-6 months beyond 10 years is very important because adequate treatments could lead to longer survival of patients with primary small-cell lung cancer.

We report herein the cases of two patients who underwent complete resection of a superior sulcus tumor (SST) plus adjuvant brachytherapy, with the area to be irradiated determined by a computer program system designed to minimize unnecessary irradiation to the normal components and to optimize the effect on the targeted area. Although the efficacy of brachytherapy on the inhibition of local relapse needs to be observed over a long period, the selective and alternative use of delivering adjuvant brachytherapy by this method appears to enhance the quality of life of patients with a SST.

Conservative sleeve resection with complete preservation of the lung parenchyma is very rarely applicable for the treatment of bronchial carcinomas. We used this surgical procedure in four patients with bronchial carcinoma in various sites of the central airway, and we obtained successful results. The pathological types were two squamous cell carcinomas and two low-grade malignant tumors (mucoepidermoid carcinoma and adenoid cystic carcinoma). If patients are properly selected, this operative procedure appears to be a safe and radical therapeutic option for the treatment of bronchial neoplasms arising from major bronchi., (Copyright 2001 S. Karger AG, Basel)

The purpose of this study was to evaluate the results of carinal resection for bronchogenic carcinoma in our institute. From 1981 to 1999, 24 carinal resection were performed for squamous cell carcinoma (n = 19), adenoid cystic carcinoma (n = 2), small cell carcinoma (n = 1), adenocarcinoma (n = 1), and mucoepidermoid carcinoma (n = 1). Nineteen underwent sleeve pneumonectomy, 2 had carinal resection without lung resection, 2 had carinal resection with right middle and lower lobectomy, and 1 had wedge pneumonectomy. In the patients with sleeve or wedge pneumonectomy, there were 5 operative death and 3 patients had survived for more than 3 years. Two patients with low-grade malignant tumors underwent carinal resection without lung resection and survived more than 10 years. We believe that limited carinal resection for low-grade malignant tumors are safe and valuable procedure. Careful selection of patients with sleeve or wedge pneumonectomy is mandatory.

Background: To the authors' knowledge, the definitions of early lung carcinoma used in Japan are not yet approved internationally. In the current study the diagnostic methods, pathology, and results of the surgical treatment of early hilar and peripheral nonsmall cell lung carcinoma cases defined by Japanese criteria are presented., Methods: Between 1977 and 1998, 43 patients with early hilar lung carcinoma were encountered. These patients constituted 14.5% of 200 hilar lung carcinoma patients who underwent resection during the same period. Between 1973 and 1998, there were 174 early peripheral lung carcinomas, which comprised 14.8% of 1173 peripheral lung carcinoma patients who underwent resection during the same period., Results: The 5-year and 10-year survival rates of the early hilar lung carcinoma were 100% and 96.9%, respectively. The majority of the patients underwent bronchoplastic surgery, such as sleeve lobectomy and parenchymal-sparing surgery including seven sleeve segmentectomies and two second carinal resections. The effectiveness of the parenchymal-sparing resections was assessed by the conventional pulmonary function test as well as perfusion and ventilation scanning. There were 174 cases of peripheral early lung carcinoma among the 218 cases of peripheral lung carcinoma with tumor dimensions of < or = 2 cm. The cell types were 142 (81.6%) cases of adenocarcinoma, 18 (10.3%) cases of squamous cell carcinoma, and 14 (8%) cases of other cell types. These 174 patients comprised 14.8% of 1173 patients with peripheral nonsmall cell lung carcinoma who underwent surgery during the same period. The 5-year and 10-year survival rates for adenocarcinoma were 89.6% and 86.8%, respectively. The 5-year and 10-year survival rates for other cell types were both 71.8%. The overall 5-year and 10-year survival rates were 86.8% and 84.6%, respectively., Conclusions: Early lung carcinoma in both the hilar and peripheral regions, is curable if it is properly diagnosed and treated.

The objective of this study was to analyze helical computed tomography (CT) findings of intrapulmonary lymph nodes (IPLNs), and to evaluate the diagnostic procedures to prevent unnecessary exploratory surgery. Between April 1997 and March 2000, we performed exploratory video-assisted thoracoscopic surgery (E-VATS) in 42 patients and in 8 patients (4 men, 4 women; 48 to 75 years of age, mean 57 years) IPLN was pathologically proven. Retrospectively, the appearances of IPLN in helical CT images were studied in detail. The diameter of the IPLNs varied from 4 to 10mm. Six nodules were located in the lower lobes and 2 nodule was in the lingula. Chest CT showed several malignancy-suggesting associated findings with pleural indentation (2/8), spicular radiation (2/8), fuzzy margins (4/8), and vascular involvement (2/8). Black colored anthracoses in 5 subpleural IPLNs were confirmed by thoracoscopy. One patient with two coin lesions was suggestive of lung metastasis of adenoidcystic carcinoma of the tongue, but one lesion was proven as IPLN, and the other as metastatic carcinoma. In conclusion, it is not possible to distinguish an intrapulmonary lymph node from a malignant lesion using the CT findings preoperatively. Therefore, a pathological study with E-VATS is necessary and sure procedure to exclude malignant disease under the present conditions.

The purpose of this study was to evaluate the results of new TNM staging system for lung cancer in 1997, especially T3N0M0, stage IIIA, stage IIIB, and pm. Five-year survival rates of the patients with stage IIIA and stage IIIB were 16% and 18% respectively (NS). Five-year survival rates of patients with T3N1M0, T1N2M0, T2N2M0, and T3N2M0 were 40%, 28%, 15%, and 3%, respectively. The prognosis of T3N2M0 was significantly worse than that of T3N1M0, T1N2M0, and T2N2M0. Five-year survival rates of the patients excluding pm 1 with T4N0M0, T4N1M0, T4N2M0, and T4N3M0 were 21%, 10%, 10%, and 0%, respectively. The prognosis of the patients with T4N0 was significantly better than that of T4N2 and T4N3. In the patients with pm, 5-year survival rates of the patients with pm 1 and pm 2 were 26% and 7%, respectively (p < 0.01). In the patients with pm 1, 5-year survival rates of the patients with N0 + N1 and N1 + N2 were 53% and 16%, respectively (p < 0.01). From our these results, we supported the new TNM system as putting T3N0M0 to stage IIB, putting pm 2 into stage IV. We proposed; 1) chest wall invasion with bone destruction stay in stage IIIA or is T4, 2) T3N1M0 is classified with stage IIB, 3) main stem bronchus invasion is classified with T2, 4) pm 1 is subdivide by N status. Furthermore, stage III seemed to be reasonably subdivided into T1-2N3M0, T4N0-1M0 as stage IIIA and T3-4N2, T1-4N3 as stage IIIB.

Objective: We examined a microdissemination of cancer cells in lymph nodes and assessed its clinical and biologic characteristics., Methods: Both primary tumors and lymph nodes (2030 nodes) were obtained from 122 patients with primary stage I lung cancer who underwent curative operations with routine systematic nodal dissection of both the hilar and the mediastinal nodes. Immunohistochemical anticytokeratin staining was used to detect nodal microdissemination of cancer cells. Vascular endothelial growth factor, vascular endothelial growth factor type C, and nm23 expression at primary sites were also immunohistochemically studied., Results: In total, 35 patients (29%) had cytokeratin-positive cells in lymph nodes. Increased expression of vascular endothelial growth factor (P =.0001) and vascular endothelial growth factor type C (P <. 0001) at primary sites were significantly associated with nodal microdissemination, and nm23 was inversely correlated with microdissemination (P =.008). The 3- and 5-year survivals for the patients with nodal microdissemination were 57% and 54%, respectively, which was a significantly worse prognosis as compared with those prognoses (83% and 76%) for the patients without nodal microdissemination (P =.006). The independent prognostic impact of nodal microdissemination was not clear; however, vascular endothelial growth factor retained independent significance., Conclusion: All of these findings lead us to conclude that the microspread of tumor cells in nodes detected by immunohistochemical anticytokeratin staining is definitely a metastasis with a high risk of systemic disease.

Background: This study provides the surgical outcome of lung cancer patients with pleural dissemination, with the assessment of the clinicopathological and biological prognostic factors., Methods: Forty-three patients who underwent operations were studied. Vascular endothelial growth factor (VEGF) and autocrine motility factor receptor (AMFR/gp78) expression was immunohistochemically evaluated., Results: In total, the overall 3 and 5-year survival rates were 31.4% and 13.1%, respectively. The patients who underwent the pleuropneumonectomy had a worse outcome than those who underwent limited operations (pleurectomy plus parenchymal resections were less than pneumonectomy). VEGF and AMFR/gp78 were highly expressed in primary tumors. Among the patients who underwent limited operations, pathological types other than adenocarcinoma and high expression of VEGF were significantly associated with a worse outcome. The pathological type was the only characteristic to retain a significant independent prognostic impact on overall survival., Conclusions: The results imply the validation of limited operation for lung cancer with pleural dissemination for the local control. High frequency of VEGF and AMFR/gp78 expression conform to the interpretation that patients with pleural dissemination have a high-risk of systemic disease.

The effectiveness of performing completion pneumonectomy (CP) to treat recurrent lung cancer was assessed in 11 patients, 6 of whom had intrapulmonary recurrence, and 5, locoregional recurrence. The pathological types of cancer were adenocarcinoma in 5 patients, squamous cell carcinomas in 5 patients, and adenoid cystic carcinoma in 1 patient. The pathological stages of the recurrent lung cancer were stage I in 8 patients, stage II in 2 patients, and stage IV in 1 patient. The microvessels in the tumors were also examined and the results compared with those in the microvessels of 61 nonrecurrent tumors. The 1- and 3-year overall survival rates after CP were 54.5% and 27.3%, respectively. The vessel densities within primary and correspondent recurrent tumors were able to be assessed in 9 patients and found to be significantly greater compared with the mean value for the nonrecurrent tumors (P < 0.0001). The vessel densities in the primary and recurrent tumors of 2 of 3 long-term survivors were found to be relatively low. These results indicate the high-grade malignant potential of recurrent tumors, which led us to conclude that the use of CP should be carefully evaluated in patients with recurrence. Assessing the vasculature in primary tumors may be a useful indicator for determining which patients could benefit from CP.