Two resected cases of benign adenomyoepithelioma.

BACKGROUND: Adenomyoepithelioma (AME) of the breast is an uncommon tumor characterized by the proliferation of ductal epithelial and myoepithelial cells with the heterogeneity. Although benign AME is relatively easy to differentiate from breast cancer by core needle biopsy (CNB) alone, a definitive diagnosis is often difficult. The imaging findings of AME are also variable, and there are particularly few reports about radiological features, including contrast-enhanced magnetic resonance imaging (MRI) and apparent diffusion coefficient (ADC) values in AME. CASE PRESENTATION: We present two cases of benign AME. Case 1 is a 30-year-old woman with a history of asthma. The cystic tumor shows smooth borders, and the intracystic solid component is irregular in shape and high vascularity. The pathological findings of the tumor were benign on CNB. The MRI scan showed a decreased ADC value. Case 2 is a 60-year-old woman with only a history of arrhythmia. The tumor shows a lobulated mass with cystic space and coarse calcifications. The pathological findings of the tumor were found to be benign by CNB. Dynamic MRI scan showed a fast washout pattern with a decreased ADC value. Both patients underwent excisional biopsy to confirm the diagnosis, and the pathological diagnosis was benign AME in both cases. CONCLUSIONS: The AME of the breast has little specific imaging information, so it can be difficult to diagnose based on pathological findings of biopsy specimen. In our case, the ADC values were exceptionally low, contrary to previous reports. It is essential to carefully diagnose AME, considering the discrepancies in imaging findings observed in this case.

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.

Malignant Melanoma of the Nipple: A Case Report.

Malignant melanoma rarely originates from the female nipple. Tumors that develop on the skin of the breast are often subject to a delayed diagnosis. Cytologic examination provides excellent diagnostic capabilities and is a safe procedure with a lower risk of local implantation, compared to needle or incisional biopsy. We herein report a patient who underwent surgical resection of a primary malignant melanoma of the nipple. An elastic soft nodule was observed on the left nipple, and no abnormal lesions were identified in the breast. Eventually, a malignant melanoma was diagnosed from the clinical and cytological evaluation findings. This bulky tumor was classified as a stage IIIC nodular melanoma, with a thickness of 12 mm. The patient received adjuvant chemotherapy and exhibits no evidence of recurrence 7 years after surgery.

Clinical performance metrics of 3D stereoscopic digital mammography compared with 2D digital mammography: observer study.

OBJECTIVE: To assess the clinical performance of three-dimensional stereoscopic digital mammography (3DsDM) compared with two-dimensional digital mammography (2DDM) for breast lesion diagnosis with jackknife free-response receiver operating characteristics (JAFROC) observer study. METHODS: 40 pairs of standard-dose 2DDM and their 3DsDM images were used for an observer performance study. A total of 18 lesions were identified as the reference standard of actionable breast lesions (Breast Imaging Reporting and Data System Category 3 or more) by two breast radiologists. Ratings and locations of "lesions" determined by observers were utilized for assessing the statistical significance of differences between eight radiologists' performances with the 2DDM images and with the 3DsDM images in jackknife free-response receiver operating characteristic analysis. RESULTS: The average figure-of-merit values for all radiologists increased to a statistically significant degree, from 0.859 with the 2DDM images to 0.936 with the 3DsDM images (p < 0.001). The average sensitivity for detecting actionable lesions was improved from 74.3 to 92.4% at a false-positive rate of 0.2 per case by use of the 3DsDM images. The mean reading time per case with 2DDM images was not significantly different from that with 3DsDM images. CONCLUSION: The use of 3DsDM would improve the observer performance for breast lesion without considerably extending the reading time. Advances in knowledge: Use of 3DsDM improves radiologists' performance for breast lesion detection.

Evaluation of the R2* value in invasive ductal carcinoma with respect to hypoxic-related prognostic factors using iterative decomposition of water and fat with echo asymmetry and least-squares emission (IDEAL).

OBJECTIVE: To correlate the R2* value obtained by iterative decomposition of water and fat with echo asymmetry and least-squares emission (IDEAL) with fibrotic focus (FF), microvessel density and hypoxic biomarker (HIF-1α) in breast carcinoma. METHODS: Forty-two patients who were diagnosed with invasive ductal carcinoma (IDC) of the breast underwent breast MRI including IDEAL before surgery. The entire region of interest (ROI) was delineated on the R2* map, and average tumour R2* value was calculated for each ROI. Histological specimens were evaluated for the presence of FF, the microvessel density (the average microvessel density and the ratio of peripheral to central microvessel density), and the grading of HIF-1α. RESULTS: FF was identified in 47.6% (20/42) of IDCs. Average R2* value for IDC with FF (42.4±13.2 Hz) was significantly higher than that without FF (28.5±13.9 Hz) (P = 0.01). Spearman rank correlation suggested that the average R2* value correlated with the grade of HIF-1α and the ratio of peripheral to central microvessel density for IDCs (P < 0.001). CONCLUSION: Quantification of tumour R2* using IDEAL is associated with the presence of FF and the overexpression of HIF-1α, and may therefore be useful in predicting hypoxia of breast carcinoma. KEY POINTS: • R2* value obtained by IDEAL correlates with the overexpression of HIF-1α. • R2* value obtained by IDEAL is associated with fibrotic focus. • R2* quantification may be useful in predicting hypoxia of breast carcinoma.

[Intrapericardial Vessel Management for Lung Cancer Surgery].

Intrapericardial vessel management is one of the necessary techniques for respiratory surgeons. We collected cases that had undergone intrapericardial vessel management for lung cancer, and herein discuss the practical performance and safety of this treatment method. We identified 23 (5.6%) of 413 patients who had undergone lung cancer surgery during the 30-month period from January 2011 to June 2013 at our institution. Twenty cases had large sized tumors near the hilum. Three cases demonstrated severe adhesion in the intrathoracic region due to a previous operation. The lung cancer staging was stage ⅠA in 1 case, stage ⅠB in 4 cases, stage ⅡB in 5 cases, stage ⅢA in 11 cases, stage ⅢB in 1 case, and stage Ⅳ in 1 case. We performed lobectomy in 11 cases, bilobectomy in 6 cases, and pneumonectomy in 6 cases. The average operation time was 366 minutes (137-965). Post operative complications were observed in five cases, including two cases of air-leakage and three cases of arrhythmia. All cases were able to walk on foot at discharge. It is important to clearly understand intrapericardial anatomy in order to carry out successful intrapericadial vessel management.

[Student education with using training simulator for endoscopic surgery].

Video-assisted thoracic surgery (VATS) has become popular in the field of chest surgery. Recently, there has been a gradual reduction in the number of surgeons in Japan, which thus increases concerns regarding a potential shortage in the number of surgeons in the future. In this study, we evaluated the efficacy of using a surgical simulator with an endoscopic simulator to provide practical training for 245 medical students. Three different tests were performed with a one-week interval between each test, and the task completion time between the 1st and 2nd training sessions was then analyzed. A reduction in the time required to perform the tasks was observed. In addition, 95% of the subjects had a positive opinion regarding the application of the device for practical training, while 85% reported an increased interest in surgery. No significant relationships were observed between the task completion time and the degree of proficiency in performing the task or between the results of students choosing to become surgeons and those not choosing to become surgeons in the future according to a follow-up study. The students who later decided to become surgeons tended to express a positive opinion on the questionnaire compared with the non-departmental staff. As a result, providing student education using a training simulator for endoscopic surgery is therefore considered to have a beneficial effect in increasing the number of medical school students who later decide to become surgeons.

Clinical Characteristics of Resected T3 Non-small Cell Lung Cancer Characterized by Parietal Pleural Invasion or Chest Wall Invasion.

This study investigated the clinicopathological characteristics and the surgical outcome in patients with non-small cell carcinoma (NSCLC) with parietal pleura invasion or chest wall invasion (p3/T3). This study clinicopathologically evaluated 760 patients who had undergone a resection for NSCLC between 1999 and 2008. There were 43 (5.7 %) patients with p3/T3 NSCLC. The patients included 37 males and 6 females. The histological types included 23 squamous cell carcinomas, 13 adenocarcinomas, 3 large cell carcinomas, 3 pleomorphic carcinomas, and 1 spindle cell carcinoma. Pneumonectomy was performed in 2 patients, bilobectomy in 1, lobectomy in 31, segmentectomy in 3, and partial resection of the lung in 6. The combined resection regions were parietal pleural in 23, ribs in 16, pericardium in 2, and diaphragm in 2 patients. Major complications included empyema in 1, chylothorax in 1, and postoperative bleeding in 1 patient. The first recurrence sites in 16 patients with recurrent disease were the lung in 5 patients, brain in 3, bone in 2, adrenal gland in 2, skin in 2, liver in 1, mesenterium in 1, mediastinal lymph node in 1, axillary lymph node in 1, and carcinomatous pleuritis in 1. The overall 5-year survival rate after surgery was 50.6 %. An en bloc resection for p3/T3 NSCLC provides a modestly favorable prognosis. Local recurrence was observed in a minority of case, and recurrence by distant metastasis was observed in most cases, suggesting a greater need for postoperative chemotherapy.

Clinical significance of the frequency of regulatory T cells in regional lymph node lymphocytes as a prognostic factor for non-small-cell lung cancer.

BACKGROUND: Regulatory T cells (Tregs) are potent immunosuppressive cells that play a crucial role in tumor immune escape. The purpose of the present study was to evaluate the prognostic significance of the frequency of CD4+CD25+Foxp3+ Tregs in the regional lymph node lymphocytes (RLNL) and peripheral blood lymphocytes (PBL) in patients who underwent surgical resection of non-small cell lung cancer (NSCLC). METHODS: The RLNL and PBL in 158 NSCLC patients who underwent complete surgical resection were collected at the time of surgery. The proportions of CD4+CD25+Foxp3+ cells in the RLNL and PBL were determined by flow cytometry. RESULTS: The average proportions of Tregs in the RLNL and PBL were 1.28% and 0.76%, respectively. The proportion of Tregs in the RLNL was significantly higher than that in the PBL (p < 0.0001). The 5-year overall survival rates of the patients according to the proportion of Tregs in the RLNL were 84.4% and 63.5% in the lower and higher groups, respectively. A significant difference was observed in the survival rate between the higher and lower groups (p = 0.0056). Among the patients with stage I disease, the 5-year survival rate (91.4%) was significantly higher in patients with the lower proportion of Tregs in RLNL that in the higher group (72.1%) (p = 0.0147). CONCLUSIONS: The higher proportion of Tregs in the RLNL was a significant unfavorable prognostic factor, even in patients with node-negative NSCLC. The information about the proportion of Tregs in the RLNL might improve the discriminatory power for assessing the risk of the recurrence of NSCLC.

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.

Pleomorphic carcinoma of the breast associated with cyst formation: a unique surgical case focusing on cytological and immunohistochemical findings. Cystic breast PC.

A mammary nodular lesion was recognized one month before the surgery in the right upper breast of a 55-year-old female. The fine needle aspiration cytology specimens contained many individual bizarre, multi-nucleated, and/or giant cells having hyperchromatic pleomorphic nuclei, prominent nucleoli, and relatively abundant cytoplasm, admixed with numerous mitotic figures in a hemorrhagic or inflammatory background. A small amount of sheet-like or three-dimensional clusters of malignant cells coexisted. We first interpreted it as high-grade malignancy, such as invasive carcinoma, not otherwise specified. A right breast-conserving surgery was performed, and gross examination revealed a cystic cavity-formed and solid tumor lesion, measuring 35 × 35 × 25 mm and looking gray-yellowish to -whitish. On microscopic examination, the tumor was composed of a diffuse proliferation of highly atypical cells devoid of adhesive characteristics, including many multi-nucleated giant bizarre cells, in a haphazard fashion with stromal invasion, alternating with sarcomatoid features of spindle tumor cells. The cystic cavity was surrounded by hemorrhagic and inflammatory granulation tissue and lined by mostly denuded but atypical tumor cells or bland-looking flattened epithelial cells. Immunohistochemically, these tumor cells are specifically positive for all epithelial markers. Therefore, we made a conclusive diagnosis of pleomorphic carcinoma of the breast with cyst formation. We should be aware that, owing to its characteristic findings, cytopathologists can diagnose correctly, based on careful cytological examination of adequate samplings. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/9290689448998782.

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.

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.

Serum level of osteopontin as a prognostic factor in patients who underwent surgical resection for non-small-cell lung cancer.

BACKGROUND: OPN is a multifunctional glycophosphoprotein originally described as a secreted protein from malignant epithelial cells. This study focused on the clinical significance of preoperative serum level of OPN in NSCLC patients who underwent a complete resection. PATIENTS AND METHODS: The serum OPN level was assayed in 244 patients who underwent a complete resection of NSCLC by commercially available sandwich enzyme-linked immunosorbent assay kits. The patients were considered as a higher group, when the serum OPN levels exceeded 81.3 ng/mL. RESULTS: The patients included 166 male and 78 female subjects. The histologic types included 172 adenocarcinomas, 49 squamous cell carcinomas, and 23 other types of carcinoma. The serum level of OPN in male patients (92.6 ng/mL) was significantly higher than that of female patients (76.9 ng/mL). The OPN level of squamous cell carcinoma was significantly higher than that of adenocarcinoma. The OPN level was significantly elevated in patients with the pleural invasion or microvascular invasion than those without the invasion. The 5-year survival rate after surgery in the lower OPN group (82.0%) was a significant favorable prognosis than that in the higher OPN group (63.7%) (P < .0001). The 5-year survival rates in the lower OPN group at stage I NSCLC (88.1%) was significantly better than that in the higher OPN group (80.5%) (P = .0321). CONCLUSION: The preoperative serum OPN level was a useful predictor of an unfavorable prognosis, and it was found to be an independent prognostic determinant of outcome in patients who underwent surgery for NSCLC.

An endobronchial lipoma successfully resected by high-frequency electric snare: a report of 2 cases.

Endobronchial lipoma is a rare, benign disease. When it causes chronic cough and pneumonia due to obstruction of the central airway, appropriate treatment is required. We herein report 2 cases of endobronchial lipoma successfully treated with a high-frequency electric snare through a flexible bronchoscope. Case 1, an 83-year-old man, visited a nearby hospital because of dyspnea on exertion. Chest computerized tomography revealed a tumor in the right main bronchus. He was referred to our hospital for further examination and treatment. Bronchoscopy showed a polypoid lesion in the right main bronchus. The tumor was resected by high-frequency electric snare through a flexible bronchoscope. Case 2 was an 83-year-old man who was diagnosed with pneumonia by a primary care physician on the basis of findings on chest computerized tomography. Bronchoscopy showed a polypoid lesion at the orifice of the right B6 bronchus, which caused segmental obstructive pneumonia. The tumor was bronchoscopically resected using a high-frequency electric snare and an neodymium-yttrium-aluminum-garnet laser. In both cases, the pathologic diagnosis was endobronchial lipoma.

Results of surgical resection for patients with thymoma according to World Health Organization histology and Masaoka staging.

OBJECTIVES: Thymomas are relatively rare tumors. In this study, we investigated the clinical features of patients who underwent surgical resection for thymoma. PATIENTS AND METHODS: This study clinicopathologically evaluated 54 consecutive patients who underwent a surgical resection of thymoma in our department between 1994 and 2006. RESULTS: A complete resection was performed in 52 patients, while two patients underwent an incomplete resection due to pleural dissemination. Combined resection with adjacent organs was performed for the lung (n=6), pericardium (n=5), and large vessels (brachiocephalic vein in three, superior vena cava in two). The concomitant autoimmune diseases were observed in 20 patients (37%), and they included myasthenia gravis in 17 patients, macroglobulinemia in one, pemphigus vulgaris in one, and stiff person syndrome in one patient. The histologic types of the World Health Organization classification diagnosed as type A in four patients, type AB in 14, type B1 in eight, type B2 in 15, and type B3 in 11. There were 27, 17, eight, and two patients with Masaoka stages I, II, III, and IV, respectively. Four patients died, and the causes of death included recurrence of thymoma in two, gastric carcinoma in one, and respiratory failure due to myasthenia gravis in one patient. The overall survival rate at 10 years was 94.6% in patients with stages I and II disease and 77.1% in patients with stages III and IV disease. CONCLUSIONS: Long-term survival can be expected not only for patients at early stages, as well as for patients with stages III and IV disease if surgical resection is completed macroscopically.

Effects of hyaluronic acid and CD44 interaction on the proliferation and invasiveness of malignant pleural mesothelioma.

Hyaluronic acid (HA) has been proposed as a biochemical marker of malignant pleural mesothelioma (MPM). The present study focused on the implications of HA and CD44 interaction in the proliferation and invasiveness of MPM. The proliferation and invasive activity was evaluated in two human mesothelioma cell lines, ACC-MESO-1 and K921MSO, by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and the transwell chamber model. The knockdown of CD44 gene expression was accomplished by transfection of the cells with small interfering RNA. Flow cytometry revealed that both the ACC-MESO-1 and K921MSO cell lines highly expressed CD44. Treatment with HA enhanced the proliferation in both mesothelioma cell lines in comparison to cells without HA treatment. The treatment with HA (25 µg/ml) also significantly upregulated the invasion of both types of cells. The silencing of CD44 significantly abrogated the effect of HA treatment on the proliferation of ACC-MESO-1 cells and significantly suppressed the proliferation of K921MSO cells. HA-CD44 binding is important for the migration and proliferation of mesothelioma cells. Therefore, the HA-CD44 interaction is a potentially useful therapeutic target in MPM.

Temporal trends in the surgical outcomes of patients with breast cancer.

BACKGROUND: The incidence of breast cancer has been increasing in Japan over the past three decades, and it is the currently the most common malignancy in Japan. This study investigated the temporal trends of the surgical outcomes in patients with breast cancer. METHODS: We evaluated 543 consecutive patients who underwent breast-cancer resection between 1980 and 2009. The temporal trends in the surgical outcome and clinicopathological features were evaluated separately for the periods covering 1980 to 1989, 1990 to 1999, and 2000 to 2009. RESULTS: The number of patients who underwent resection during these three respective periods were 133, 176, and 234, respectively. All patients were women. The percentage of patients at stages 0 or 1 was 63.2%, 58.5%, and 43.6%, respectively, during the three periods. The mean diameter of tumors in each period was 38, 29, and 30 mm, respectively. The percentage of tumors with positive ER expression was 62.5%, 64.3%, and 69.7%, respectively. In terms of surgical procedures, the use of Halsted's radical mastectomy decreased during each period: from 40.6% of cases to 8.5% and then to 0.4%, while the proportion of breast-conserving therapies increased, from 0% to 12.5%, and finally to 35.9%. The postoperative 10-year survival rates during the three periods were 75.9%, 83.5%, and 84.9%, respectively. The 10-year survival rates of patients with stage II disease during the three periods were 66.2%, 75.7%, and 90.7%, respectively. The prognosis of stage III disease in the three periods also showed a tendency toward improvement, increasing from 37.8% to 64.2%, and finally to 84.5%. CONCLUSION: The survival of patients with stage II and III disease has improved during the past 30 years. Along with the recent advances in drug therapy, the surgical treatment has become less invasive, often because of drug therapy-related modifications.

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.

[Clinical characteristics of pulmonary hamartoma resected surgically as undiagnosed pulmonary nodule].

Pulmonary hamartoma is the most common tumor in benign lung neoplasm. We reviewed the clinical characteristics of 9 patients who had undergone surgical resection for pulmonary hamartoma between 2000 and 2009. There were 1 male and 8 female patients. The age of the patients ranged from 42 to 77 years old (mean 59). Calcification was not observed by computed tomography scan except in 1 patient. Although transbronchial lung biopsy (TBLB) was performed in 5 patients, no definitive diagnosis was obtained. Six patients underwent 18F-fluorodeoxyglucose (FDG)-positron emission tomography, and none of them showed any accumulation of FDG except for 1 patient. Concerning the operative procedures, a sleeve lobectomy was performed in 1 patient, a segmentectomy in 1, a lobectomy in 2, a partial resection of the lung in 3, and a nucleation in 2 patients. The postoperative courses were uneventful, and no findings of recurrence were observed in any of the patients after surgery. As a preoperative diagnosis of pulmonary hamartoma is often difficult in TBLB, it is necessary to perform surgical resection in the differential diagnosis of lung cancer or metastatic lung tumor, unless there are typical findings of pulmonary hamartoma in clinical imaging.