Development of adoptive immunotherapy with KK-LC-1-specific TCR-transduced γδT cells against lung cancer cells.

The present study analyzed the antitumor effect of γδT cells transduced with the TCR of cancer-specific CTLs to establish forceful cancer-specific adoptive immunotherapy. We cloned the TCRαß genes from CTLs showing HLA-B15 restricted recognition of Kita-Kyushu lung cancer antigen-1 (KK-LC-1), a cancer/germline gene antigen, identified in a lung adenocarcinoma case (F1121). The TCRαß and CD8 genes were transduced into γδT cells induced from PBLs of healthy volunteers stimulated with zoledronate and IL-2. The KK-LC-1-specific TCRαß-CD8 γδT cells showed cytotoxic activity against the KK-LC-1 positive lung cancer cell line F1121L and produced IFN-γ against F1121L and KK-LC-1 peptide-pulsed F1121 EBV-B cells. These responses were blocked by HLA class I and HLA-B/C antibodies. An in vivo assay using NOD/SCID mice with xenotransplantation of human lung cancer cells was performed, and the TCRαß-CD8 transduced γδT cells (TCRαß-CD8 γδT cells) were intravenously injected. Growth inhibition of KK-LC-1+ , HLA-B15+ lung cancer cells was confirmed in mice with injection of the TCRαß-CD8 γδT cells from 1 wk after xenotransplantation of cancer cells but not in those treated 2 wk after xenotransplantation. The resected specimens of the tumor, 2 wk after xenotransplantation, highly expressed FasL but not programmed death ligand-1 (PD-L1) by immunohistochemical staining. FasL highly expressed cancer cells xenotransplanted 2 wk ago were resistant to TCRαß-CD8 γδT cells injection. These results suggested that apoptosis of Fas-positive TCRαß-CD8 γδT cells may be induced by a Fas-mediated signal after interacting with FasL-positive cancer cells.

Clinical significance of expression of cancer/testis antigen and down-regulation of HLA class-I in patients with stage I non-small cell lung cancer.

AIM: The purpose of this study was to investigate the clinical significance of expression of cancer/testis (CT) antigen and down-regulation of HLA class-I in patients with stage I non-small cell lung cancer (NSCLC), which underwent complete surgical resection. PATIENTS AND METHODS: The expression of HLA class-I molecules was evaluated in 136 resected NSCLC specimens by immunohistochemistry. The results were scored as the percentage of stained tumor cells and categorized into two groups: 0-79%, reduced expression; and >80%, normal expression. The expression of CT antigen was performed by reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: The expression of HLA class-I was normal in 49 tumors (36%), and there was reduced expression in 87 tumors (64%). The expression of Melanoma antigen (MAGE)-A3, MAGE-A4, and Kita-Kyushu lung cancer antigen-1 (KK-LC-1) was positive in 34 (25.0%), 22 (16.2%), and 42 (30.9%) patients, respectively. There was no significant difference in the proportion of HLA class-I expression associated with the expression of any of the CT antigens. Among the patients with positive expression of at least one of the CT antigens, the 5-year survival rate of the patients with the normal expression of HLA class-I was 87.5%; however, it was 63.4% in patients with the reduced expression of HLA class-I (p=0.0477). CONCLUSION: Reduced expression of HLA class-I was an unfavorable prognostic factor in patients with positive expression of CT antigen, and represents an important hurdle to antigen-based cancer immunotherapy.

Natural human plasmacytoid dendritic cells induce antigen-specific T-cell responses in melanoma patients.

Vaccination against cancer by using dendritic cells has for more than a decade been based on dendritic cells generated ex vivo from monocytes or CD34(+) progenitors. Here, we report on the first clinical study of therapeutic vaccination against cancer using naturally occurring plasmacytoid dendritic cells (pDC). Fifteen patients with metastatic melanoma received intranodal injections of pDCs activated and loaded with tumor antigen-associated peptides ex vivo. In vivo imaging showed that administered pDCs migrated and distributed over multiple lymph nodes. Several patients mounted antivaccine CD4(+) and CD8(+) T-cell responses. Despite the limited number of administered pDCs, an IFN signature was observed after each vaccination. These results indicate that vaccination with naturally occurring pDC is feasible with minimal toxicity and that in patients with metastatic melanoma, it induces favorable immune responses.

Intrapleural chemotherapy improves the survival of non-small cell lung cancer patients with positive pleural lavage cytology.

PURPOSE: Information regarding the treatment of pleural lavage cytology (PLC)-positive patients is still limited. This study evaluated the efficacy of intrapleural chemotherapy (IPC) in PLC-positive patients. METHODS: Three hundred eighty-six of the 567 lung cancer patients who underwent surgery had undergone PLC after thoracotomy, following by a complete resection were evaluated. IPC was performed after surgery, and cisplatin or adriamycin was injected intrapleurally through the thoracic tube. RESULTS: The pathological diagnosis showed that 17 patients (4.4 %) were positive for (or suspected to have) malignancy in their PLC. The univariate and multivariate analysis showed that only pleural invasion was a significant predictor of a PLC-positive status. The 5-year overall survival in PLC-positive patients was 38 % and that in PLC-negative patients was 84 %. Both the univariate (p < 0.01) and multivariate (p = 0.045) analyses showed that the status of PLC was significantly associated with the overall survival. Eight of the 17 PLC-positive patients underwent IPC. The 2-year OS rate in the patients treated with IPC was 88 % and that of those without IPC was 44 (p = 0.04). CONCLUSION: IPC improved the postoperative survival in PLC-positive NSCLC patients, and a further prospective evaluation regarding this therapy is warranted.

Prognostic implications of human leukocyte antigen class I expression in patients who underwent surgical resection for non-small-cell lung cancer.

BACKGROUND: The purpose of the present study was to clarify the prognostic significance of human leukocyte antigen (HLA) class I expression in patients with non-small-cell lung cancer who underwent complete surgical resection. PATIENTS AND METHODS: The expression of HLA class I molecules was evaluated in 403 resected NSCLC specimens using immunohistochemistry. The results were scored as the percentage of stained tumor cells and were categorized into three groups: 0%-24% (decreased), 25%-79% (heterogeneous), and 80% or more (normal). RESULTS: The expression of HLA class I was evaluated in 124 tumors in the normal expression group, 181 tumors in the heterogeneous expression group, and 98 tumors in the decreased expression group. The 5-year survival rate of all patients after surgery according to the HLA class I expression in the normal, heterogeneous, and decreased groups was 76.6%, 65.9%, and 76.1%, respectively. The prognosis was significantly better in the normal expression group than in the heterogeneous group. Normal HLA class I expression also correlated with favorable survival in patients with stage I disease. CONCLUSIONS: The normal expression of HLA class I was associated with a favorable prognosis compared with the heterogeneous expression group, but no significant difference was observed between the normal expression and decreased expression groups.

Cancer/testis antigen expression as a predictor for epidermal growth factor receptor mutation and prognosis in lung adenocarcinoma.

OBJECTIVES: Immune therapy targeting cancer/testis (CT) antigens improve the survival in several types of solid tumours. The expression of CT antigens is related to poor survival in non-small-cell lung cancer (NSCLC). The epidermal growth factor receptor (EGFR) mutation is the best predictive factor for the sensitivity to tyrosine kinase inhibitors in lung adenocarcinoma. The aim of this study was to elucidate the correlation between the expression of CT antigens and clinicopathological factors, including the EGFR mutation, and to analyse the prognosis in lung adenocarcinoma. METHODS: Data were collected from a total of 281 lung adenocarcinoma patients who underwent surgery. Among them, 125 cases, whose specimens were too small to extract sufficient DNA and/or RNA, and 2 cases with the coexistence of another histological lung cancer were excluded. A total of 154 patients were reviewed. The expression of CT antigens (melanoma-associated antigen gene [MAGE]-A4 and KK-LC-1) and the EGFR-activating mutation (L858R point mutation in exon 21 and inframe deletion in exon 19) was evaluated by using polymerase chain reaction amplification. RESULTS: The expression of MAGE-A4 and KK-LC-1 was detected in 14 (9%) and 54 patients (35%) with adenocarcinoma. The EGFR-activating mutation was found in 64 patients (42%). Univariate and multivariate analyses demonstrated that tumours expressing at least one CT antigen were associated with no EGFR mutation (odds ratio = 0.3; 95% confidence interval, 0.14-0.71; P < 0.01). A survival analysis was performed in 135 patients who underwent complete resection and the 5-year overall survival rate was 71.1% in those with any expression of CT antigens and 83.2% in those without expression of the genes (P < 0.04). CONCLUSION: Two different therapeutic targets, EGFR-activating mutation and CT antigen, have a negative relationship with each other.

Clinical significance of human leukocyte antigen loss and melanoma-associated antigen 4 expression in smokers of non-small cell lung cancer patients.

BACKGROUND: Melanoma-associated antigen-A4 (MAGE-A4) is one of the candidates for a target of immunotherapy and is expressed in non-small cell lung cancer (NSCLC). However, tumors sometimes lose human leukocyte antigen (HLA) class I expression, and tumor-specific T cells cannot eliminate the tumor with loss of HLA. However, the relationship between MAGE-A4 expression and HLA loss has remained unclear. METHODS: Among 363 NSCLC patients who consecutively underwent curative surgery, 187 cases whose material could be analyzed were reviewed. The expression of HLA class I molecules was assessed by immunohistochemical staining. The expression of MAGE-A4 was analyzed by RT-PCR. RESULTS: Seventy-seven tumors expressed HLA normally; however, 110 tumors lost HLA. The proportion of patients with a smoking habit and expressing the MAGE-A4 gene in patients with HLA loss was higher than those with HLA expression (p = 0.04 and 0.028, respectively). Five-year overall survival (OS) rate in the patients expressing MAGE-A4 but with loss of HLA was 52.4 %, and OS was significantly poorer than their counterparts (74.0 %, p = 0.036). Multivariate analysis indicated that advanced stage or history of smoking and HLA loss was an independently poor prognostic predictor of OS in NSCLC (p < 0.01 and p = 0.04, respectively). CONCLUSION: HLA class I loss in NSCLC was related to smoking history and MAGE-A4 expression of tumors. HLA class I loss in smokers or patients with the MAGE-A4 gene was a prognostic factors in NSCLC.

Immunosuppressive effect of regulatory T lymphocytes in lung cancer, with special reference to their effects on the induction of autologous tumor-specific cytotoxic T lymphocytes.

It is not easy to induce cytotoxic T lymphocytes (CTLs) against cancer in in vitro culture. Regulatory T cells (Tregs) are considered to play a pivotal role in tumor immune escape. In this study, we analyzed the distribution of Tregs among tumor-infiltrating lymphocytes (TILs), regional lymph node lymphocytes (RLNLs) and peripheral blood lymphocytes (PBLs) in patients with lung cancer, and analyzed the effect of Tregs on the induction of CTLs in vitro. A total of 84 patients with non-small cell lung cancer underwent surgery between January 2003 and December 2004. The TILs, RLNLs and PBLs from these patients were subjected to a comparison analysis. The proportion of CD4(+)CD25(+)Foxp3(+) cells in these lymphocytes was determined by flow cytometry. The effects of Tregs on the induction of CTLs was analyzed by the depletion of Tregs in mixed lymphocyte-tumor cell culture (MLTC). The average proportions of Tregs in the TILs, RLNLs and PBLs were 10.4±9.5, 4.4±2.4 and 2.8±2.1%, respectively. The proportion of Tregs in the RLNLs was significantly higher than that in the PBLs (P<0.001); furthermore, TILs contained a larger number of Tregs than RLNLs (P=0.034). These Tregs substantially suppressed the induction of CTLs against autologous tumor cells. The depletion of Tregs in the MLTC resulted in the successful induction of CTLs. Tregs were found at a higher frequency in the TILs and RLNLs than in the PBLs in lung cancer patients. Since Tregs inhibited the induction of CTLs, the depletion of Tregs may represent a new therapeutic strategy for lung cancer patients.

Basaloid carcinoma of the lung associated with central cavitation: a unique surgical case focusing on cytological and immunohistochemical findings.

A history of an increase in pulmonary mass was presented in the right upper lobe of a 72-year-old male. The bronchial brushing cytology specimens contained many sheet-like or three-dimensional clusters of malignant cells having small to medium-sized, uniform oval to round, and hyperchromatic nuclei, inconspicuous nucleoli, and scanty cytoplasm, admixed with mitotic figures. A coarsely granular chromatin pattern was predominantly noted. We first interpreted it as suspicious of malignancy, such as atypical carcinoid. A right upper lobectomy was performed, and gross examination revealed a centrally cavity-formed tumor lesion, containing asymmetrically thinned wall and looking grayish to whitish, partly adjacent to the bronchiolar wall. On microscopic examination, the tumor was predominantly composed of a solid proliferation of atypical epithelial cells without apparent glandular or squamous differentiation, often arranged in an alveolar growth pattern with peripheral palisading. Immunohistochemically, these atypical cells are negative for all three neuroendocrine markers and thyroid transcription factor 1, whereas positive for 34ßE12, p63 and S-100 protein. Therefore, we finally made a diagnosis of basaloid carcinoma with cavity formation. We should be aware that, owing to its characteristic features, cytopathologists might be able to raise basaloid carcinoma of the lung as one of differential diagnoses, based on careful cytological examination. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.dianosticpathology.diagnomx.eu/vs/1519986488570234

Prognostic factors before and after recurrence of resected non-small cell lung cancer.

BACKGROUND: The post-surgical follow-up strategy in non-small cell lung cancer (NSCLC) is still controversial. Data on factors that affect the interval between surgery and recurrence or predict survival after recurrence in NSCLC patients are still limited. METHODS: From a group of 775 NSCLC patients who consecutively underwent curative surgery, 133 patients showing recurrence were retrospectively analyzed. RESULTS: Recurrence was most often seen in smokers and patients with advanced stage disease. In patients experiencing relapse, the 1- and 2-year recurrence rates were 58% and 84%, respectively. A multivariate analysis showed that patients who underwent limited surgery, had non-adenocarcinoma disease, or had metastatic lymph node involvement showed early recurrence (p-values: <0.01, 0.04, and 0.04, respectively). Among all relapsed patients, the 2-year overall survival rate after recurrence was 37%. A multivariate analysis demonstrated that patients with lymph node metastasis at the time of surgery and patients who experienced early recurrence were significantly more likely to have a shorter survival time after recurrence (hazard ratio, 1.73; p=0.03; hazard ratio, 2.56; p<0.001, respectively). CONCLUSIONS: Patients who are node-positive, show non-adenocarcinoma disease, and/or undergo limited surgery should receive careful follow-up during the first year after surgery for NSCLC. The present data provide additional information about postoperative recurrence in NSCLC patients.

Antitumor activity of human γδ T cells transducted with CD8 and with T-cell receptors of tumor-specific cytotoxic T lymphocytes.

The difficulty in the induction and preparation of a large number of autologous tumor-specific cytotoxic T lymphocytes (CTL) from individual patients is one of major problems in their application to adoptive immunotherapy. The present study tried to establish the useful antitumor effectors by using γδ T cells through tumor-specific TCRαß genes transduction, and evaluated the efficacy of their adoptive transfer in a non-obese diabetic/severe combined immunodeficiency (NOD/SCID) mice model. The TCRαß gene was cloned from the HLA-B15-restricted CTL clone specific of the Kita-Kyushu Lung Cancer antigen-1 (KK-LC-1). The cloned TCRαß as well as the CD8 gene were transduced into γδ T cells induced from peripheral blood lymphocytes (PBL). Cytotoxic T lymphocyte activity was examined using a standard 4 h (51) Cr release assay. Mice with a xenotransplanted tumor were treated with an injection of effector cells. Successful transduction of TCRαß was confirmed by the staining of KK-LC-1-specific tetramers. The γδ T cells transduced with TCRαß and CD8 showed CTL activity against the KK-LC-1-positive lung cancer cell line in a HLA B15-restricted manner. Adoptive transfer of the effector cells in a mice model resulted in marked growth suppression of KK-LC-1- and HLA-B15-positive xenotransplanted tumors. Co-transducing TCRαß and CD8 into γδ T cells yielded the same antigen-specific activity as an original CTL in vitro and in vivo. The TCRαß gene transduction into γδ T cells is a promising strategy for developing new adoptive immunotherapy.

The tumour shape of lung adenocarcinoma is related to the postoperative prognosis.

We evaluated the tumour shape as a potential prognostic indicator in lung adenocarcinoma patients. Among 994 patients who underwent curative surgery, 78 cases of adenocarcinoma (N0M0) with tumours ≥ 31 mm in diameter were reviewed. The patients were divided into two groups based on the ratio between the longest and the smallest axis length. The patients who had tumours whose ratios were > 0.5 were defined as the globular shape group (GL) and the others, whose ratio was 0.5 or less, were defined as the ellipse shape group (EL). The 78 patients were divided into two subgroups (57 in the GL and 21 in the EL). The tumour shape was related to the prognosis, and the 5-year overall survival (OS) rate in the GL was 51.5%, and that in the EL was 85.5% (P = 0.018). The 5-year disease-free survival rate of the GL was 46.6% and that of the EL patients was 85.0% (P = 0.04). The multivariate analysis showed that the shape of the tumour and the presence of pleural invasion were the independent and significant factors predicting the OS (P = 0.04 and P < 0.01, respectively). In adenocarcinoma patients, the shape of the tumour is related to the postoperative survival.

Hypotension due to Chemotherapy in a Patient with Small Cell Lung Cancer and Lambert-Eaton Myasthenic Syndrome Undergoing Hemodialysis: A First Case Report.

We present the first case of small cell lung cancer with Lambert-Eaton myasthenic syndrome during hemodialysis (HD). A 72-year-old male patient receiving HD experienced progressive muscle weakness. He was diagnosed with small cell lung cancer with Lambert-Eaton myasthenic syndrome due to an increased serum level of anti-voltage-gated calcium channel antibody and aspiration cytology on endobronchial ultrasonography for the swelling of a subcarinal lymph node. He received chemotherapy consisting of carboplatin (300 mg/m(2)) and etoposide (50 mg/m(2)), to which he had a partial response. However, the second therapy course could not be administered because of the unexpected development of severe hematological adverse events, which also prevented him from undergoing further HD. This case indicates that caution should be taken when using chemotherapy for such patients because of hypotension due to chemotherapy, with which it is impossible to undergo HD.

Survival impact of node zone classification in resected pathological N2 non-small cell lung cancer.

We assessed the prognostic value of the 'Zone-classification' which has been proposed by the Japanese Association for Lung Cancer (JALC) for mediastinal nodal metastases in non-small cell lung cancer (NSCLC). Among 357 NSCLC patients who underwent curative surgery, 46 patients with pathological (p) N2 disease were divided into two groups as follows: 32 patients in whom the nearer zone was involved were classified as the pN2a-1 group, and 14 patients in whom the further mediastinal node station was involved were classified as the pN2a-2 group. The proportions of patients with non-adenocarcinoma histology, with multiple station metastases with the involvement of four or more nodes, and who underwent pneumonectomy, were higher in the pN2a-2 group. The 'Zone-classification' proved to be a significant prognostic factor in a univariate analysis (the 5-year overall survival rate, 7.1% for pN2a-2 versus 21.9% for pN2a-1; P < 0.01). A multivariate analysis confirmed that pN2a-2 sub-classification (hazard ratio 2.77; P = 0.03) and undergoing pneumonectomy (hazard ratio 4.86; P < 0.01) were independent and significant factors in predicting a poor prognosis. In pN2 NSCLC patients, the involved mediastinal zone according to the primary tumour site was important in prediction of survival.

Differences in sensitivity to tumor-specific CTLs between primary and metastatic esophageal cancer cell lines derived from the same patient.

PURPOSE: MHC antigens and adhesion molecules, such as the intracellular adhesion molecule (ICAM-I), play an important role in cellular immune response. We examined the expression patterns of these molecules in both primary and metastatic esophageal carcinoma cells from the same patient and evaluated the cellular immune responses against these cells. MATERIALS AND METHODS: In the esophageal cancer patient (H122), tumor cell lines were established from primary and subcutaneous metastatic lesions. We compared the expression of cell surface molecules on the metastatic tumor cell line (H122SC) with that on the primary tumor cell line (H122ESO) using flow cytometry. Moreover, we analyzed the differences in cellular immune responses against these cell lines, which expressed similar levels of the Tara antigen, using the Tara antigen-specific CTL clone. RESULTS: H122SC ICAM-1 expression was significantly lower in H122ESO, and the Tara antigen-specific CTL clone produced lower levels of TNF in response to H122SC than H122ESO. ICAM-1 transfection into the H122SC rendered these cells as sensitive to the CTL clone as the H122ESO. CONCLUSION: The metastatic tumor cells displayed lower regulated ICAM-1 expression levels and were less sensitive to specific CTLs. ICAM-1 downregulation may be one mechanism by which tumor cells escape immunologic surveillance.

Pleural lavage cytology immediately after thoracotomy in patients with completely resected non-small cell lung cancer.

This study evaluated 325 patients who had undergone pleural lavage cytology (PLC) immediately after thoracotomy following a complete resection for non-small cell lung cancer (NSCLC) between 2004 and 2008. The number of patients with negative and positive findings in PLC was 309 and 13, respectively. The proportion of T1 in the PLC-positive group was significantly smaller than that of the PLC-negative group. The pathologic examinations revealed that the parietal pleural invasion was significantly more severe in the PLC-positive group than in the PLC-negative group. Pathologic lymphovascular invasion was also significantly more prominent in the PLC-positive group than in the PLC-negative group. The 5-year survival rate after surgery in the PLC-positive group and PLC-negative group was 54.7% and 79.0%, respectively. The positive finding in PLC showed a tendency of an unfavorable prognosis for NSCLC patents following complete resection. Further clinical studies will be necessary to evaluate the efficacy of adjuvant therapy for PLC-positive patients.

[Management of patients with bronchial foreign bodies].

The aspiration of foreign bodies into the bronchus frequently occurs in children as well as in elderly people. Foreign bodies in the airway not only cause chronic cough and pneumonia, but also result in life-threatening conditions, such as dyspnea and cyanosis. This report presents the clinical characteristics of 6 patients with bronchial foreign bodies who were treated between 2006 and 2010, including 4 male and 2 female patients. The age of the patients ranged from 8 to 83 years old. Foreign bodies were located in the right bronchial tree in all the patients. Chest X-rays showed pneumonia or atelectasis in 5 out of 6 patients. The foreign bodies were an artificial teeth or a tooth in 5 patients, and a fish bone in 1 patient. Five patients had fiberoptic bronchoscopy under local anesthesia, although an 8-year-old girl required general anesthesia with a laryngeal mask. Surgery was needed in only one case. Bronchial foreign bodies present a large range of symptoms, from trivial symptoms to irreversible damage to the bronchus and the lung, which can be life threatening. Nonspecific respiratory symptoms may be mistakenly attributed to other medical diagnoses unless there is a clear history of aspiration. However, an early diagnosis is very important, because inflammatory granulation due to long-term impaction of foreign bodies makes its removal difficult.

Preoperative CYFRA 21-1 and CEA as prognostic factors in patients with stage I non-small cell lung cancer.

PURPOSE: This study investigated the preoperative serum levels of CYFRA 21-1 and CEA as prognostic factors in patients with stage I non-small cell lung cancer. SUBJECTS: This study evaluated 341 patients who had undergone a complete resection for stage I NSCLC between 2002 and 2008. RESULTS: The patients included 193 males and 148 females. The mean age of the patients was 69.2 years (range: 19-88). The histological types included 264 adenocarcinomas, 56 squamous cell carcinomas, 11 large cell carcinomas, and 10 other types of carcinoma. A pneumonectomy was performed in 2 patients, a bilobectomy in 7, a lobectomy in 255, a segmentectomy in 46, and partial resection of the lung in 31 patients. The positive rates for CYFRA 21-1 in the adenocarcinoma and squamous cell carcinoma patients were 33.3% and 76.8%, respectively. The positive rates for CEA in adenocarcinoma and squamous cell carcinoma patients were 23.8% and 26.8%, respectively. The 5-year survival rate after surgery in the normal CYFRA 21-1 group and the high CYFRA 21-1 groups were 92.8% and 75.4%, respectively, in the patients with stage I NSCLC. There was a significant difference between the 2 groups (p<0.0001). The 5-year survival rate according to the serum level of CEA in the patients with stage I NSCLC were 88.3% for the normal group and 76.3% for the high group. In a multivariate analysis using the variables found to be significant prognostic factors in univariate analysis, a high CYFRA 21-1 level was found to be a significant independent prognostic factor (95% confidence interval 1.213-5.442, p=0.014). CONCLUSION: A high preoperative CYFRA 21-1 level was a significant independent prognostic factor in patients with stage I NSCLC. The patients with a high CYFRA 21-1 level should carefully followed-up to rule out occult metastasis. Further clinical studies will be necessary to evaluate the efficacy of adjuvant therapy for the patients selected according to this criterion.

[Clinical analysis of esophageal cancer associated with other primary cancers].

This study aims to investigate the therapeutic and prognostic implications of esophageal cancer in patients with other primary cancer. Between April 1992 and December 2008, in 83 patients underwent surgery for esophageal cancer at our department. Among them, 24 patients (28.9%) had medical history of additional primary cancer. There were 16 metachronous cancers and 8 synchronous cancers. Six patients had antecedent other primary cancers, and subsequent primary cancers developed in 10 patients. The other primary cancers included head and neck cancer in 8 patients, gastric cancer in 8, lung cancer in 6, colorectal cancer in 3, and other cancer in 3. The patients with other primary cancers were both heavy smokers and heavy drinkers in comparison to those without other primary cancers. The post-operative 5-year survival rate in patients with subsequent cancers, antecedent cancers, and synchronous cancers were 100%, 70.0%, and 46.9%. The 5-year survival rate was 33.4% in patients without other primary cancers. A high incidence of multiple primary cancers was observed in patients with esophageal carcinoma but the prognosis of these patients with metachronous cancers are better than that of patient with synchronous cancers and patients without other primary cancers. Post-operative follow up is considered to be necessary for early detection of multiple occurrences of carcinoma, especially in the upper aerodigestive tract.

[Surgical treatment for patients with pulmonary sclerosing hemangioma].

Sclerosing hemangioma of the lung, a rare disease, is a low grade malignancy possibly originating from type II pneumocytes or Clara cells. We report the clinical characteristics of 8 patients who underwent surgical resection for sclerosing hemangioma between 2005 and 2010 in our hospital. All cases were female, and the average age was 50 (range: 28-83) years old. The median tumor doubling time was 965 days, suggesting they were slowly growing tumors. In the present cases, five patients had another lung disease: lung cancer in two, metastatic lung tumor in one and atypical adenomatous hyperplasia in two patients. Intraoperative frozen section examinations were performed in seven cases. Five patients were diagnosed correctly, but two patients were diagnosed with adenocarcinoma and organizing pneumonia. As a clinical characteristics, sclerosing hemangioma in the present study showed well-demarcated and slow-growing tumor. The postoperative clinical courses of all cases were uneventful, and no findings of recurrence distant metastasis, lymph node metastasis and local recurrence after surgery were observed in any of the patients.