Paraneoplastic limbic encephalitis due to lung squamous cell carcinoma.

Paraneoplastic limbic encephalitis (PLE) is one of paraneoplastic neurological syndrome (PNS). We herein report a case of PLE due to lung squamous cell carcinoma. A 80-year-old woman visited because of several neurological symptoms. Brain magnetic resonance imaging revealed hyperintense signals at the splenium of the corpus callosum, suggesting limbic encephalitis. Chest X-ray and computed tomography showed a 17 × 14 mm tumor in the left lung field, suggesting lung cancer. Surgical examination revealed T1bN0M0 lung squamous cell carcinoma. She died 50 days after surgery due to the rapid progression of encephalitis. PLE is an extremely rare disorder, and even a case in the early stage of cancer shows poor prognosis. We should doubt a possibility of PLE, and detailed brain examination should be performed in case of consciousness disorder with rapid progression in the cancer patient.

[ST Segment Elevation on Electrocardiogram (ECG) during Pleural Lavage with Distilled Water;Report of a Case].

Pleural lavage with distilled water is often employed in lung resection to eliminate malignant cells. Here we report a case of transient ST segment elevation on electrocardiogram (ECG) during pleural lavage with distilled water. A 73-year-old female was referred to our hospital because of an abnormal shadow on a chest roentogenogram. Chest computed tomography scan revealed a mass in left S4+5 segment of left upper lobe. It was proved to be adenocarcinoma of the lung by transbronchial lung biopsy and she underwent left upper lobectomy. During pleural lavage with distilled water, ST segment was elevated on ECG. In this case, it was because that the pericardium was excised and the myocardium was exposed to distilled water during pleural lavage.

Pleural dissemination of a mixed ground-glass opacity nodule treated as a nontuberculous mycobacterial infection for 6 years without growing remarkably.

Pulmonary ground-glass opacity (GGO) nodules, which do not grow remarkably, are often observed without treatment. Lung tumors coexisting with inflammation and infection are difficult to diagnose. In this paper, we describe a very rare case of a pulmonary mixed GGO nodule with pleural dissemination. In 67-year-old female, chest computed tomography (CT) showed a mixed GGO nodule that had not grown remarkably in the right lung. For 6 years, the mixed GGO had been treated as nontuberculous mycobacterial infection. She was referred to our department for further investigation of the mixed GGO. We suspected lung cancer and performed lung segmentectomy. The tissue showed pleural dissemination. Coexisting nontuberculous mycobacteria (NTM) delayed the clinical diagnosis. Peripheral lung nodules should be resected or diagnosed as soon as possible, despite manifesting as a slow growth.

Primary Adenoid Cystic Carcinoma of the Peripheral Lungs.

We herein report a very rare case of adenoid cystic carcinoma of the peripheral lungs. A 77-year-old female visited a family physician for aortitis syndrome, diabetes mellitus and hyperlipidemia. A follow-up chest computed tomography scan for aortitis syndrome revealed a nodule in the middle lobe of the right lung. Although a transbronchial lung biopsy was attempted, a definitive diagnosis could not be made. Because the possibility of lung malignancy could not be ruled out, thoracoscopic wedge resection of the middle lobe was performed. The intraoperative pathological diagnosis revealed carcinoma of the lungs and we performed middle lobectomy under complete video-assisted thoracoscopic surgery. A histopathological examination demonstrated an adenoid cystic carcinoma with a characteristic cribriform structure.

[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.

Epidermal growth factor receptor-GEP100-Arf6 axis affects the prognosis of lung adenocarcinoma.

The overexpression of Arf6 and GEP100 is responsible for the invasive activity that is crucial for the activation of the epidermal growth factor receptor (EGFR) signaling pathways in human cancer. However, whether or not the expression of the EGFR-GEP100-Arf6 axis can be used as a biomarker for the prognosis of lung cancer has yet to be fully determined. Tumor specimens were collected from 182 patients who underwent a complete resection for lung adenocarcinoma. We analyzed phospho-EGFR (p-EGFR), GEP100, and Arf6 expression levels in the primary tumor by immunohistochemical analysis. The expression of p-EGFR, GEP100, and Arf6 was observed in 65 (35.7%), 95 (52.2%), and 20 (11.0%) patients, respectively. Significant associations between p-EGFR and GEP100 expression and vessel invasion were identified. The expression of these individual molecules was not associated with any statistically significant differences in survival. However, triple positive expression of p-EGFR, GEP100, and Arf6 was significantly associated with an increased risk of death based on the multivariate analysis. The EGFR-GEP100-Arf6 axis affected the prognosis of patients with primary lung adenocarcinoma. The combination of p-EGFR, GEP100, and Arf6 staining can predict the prognosis of patients after surgery.

Discrepancy between the Clinical Image and Pathological Findings of Non-Small Cell Lung Cancer Harboring an Epidermal Growth Factor Receptor Gene Mutation That Was Surgically Resected after Gefitinib Treatment.

We herein describe a discrepancy between the clinical image and pathological findings in a non-small cell lung cancer patient with an epidermal growth factor receptor (EGFR) mutation who underwent surgical resection after gefitinib treatment. The patient was a 66-year-old female with c-stage IIIA lung adenocarcinoma harboring an EGFR gene mutation; she was surgically treated after receiving gefitinib. The pathological examination revealed adenocarcinoma, and the pathologically therapeutic effect was considered to be slight or of no response. EGFR T790M mutation and MET amplification were not present. The pathologically therapeutic effect is generally well correlated with the response rate after induction therapy. In this case, there was a discrepancy between the clinical image and pathological findings. Our findings, therefore, raise questions about the role of surgery after EGFR-tyrosine kinase inhibitor treatment.

Evaluation of undiagnosed solitary lung nodules according to the probability of malignancy in the American College of Chest Physicians (ACCP) evidence-based clinical practice guidelines.

BACKGROUND: This study retrospectively investigated the clinical significance of undiagnosed solitary lung nodules removed by surgical resection. PATIENTS AND METHODS: We retrospectively collected data on the age, smoking, cancer history, nodule size, location and spiculation of 241 patients who had nodules measuring 7 mm to 30 mm and a final diagnosis established by histopathology. We compared the final diagnosis of each patient with the probability of malignancy (POM) which was proposed by the American College of Chest Physicians (ACCP) guidelines. RESULTS: Of the 241 patients, 203 patients were diagnosed to have a malignant lung tumor, while 38 patients were diagnosed with benign disease. There were significant differences in the patients with malignant and benign disease in terms of their age, smoking history, nodule size and spiculation. The mean value and the standard deviation of the POM in patients with malignant tumors were 51.7 + 26.1%, and that of patients with benign lesions was 34.6 + 26.7%. The area under the receiver operating characteristic (ROC) curve (AUC) was 0.67. The best cut-off value provided from the ROC curve was 22.6. When the cut-off value was set at 22.6, the sensitivity was 83%, specificity 52%, positive predictive value 90%, negative predictive value 36% and accuracy 77%, respectively. CONCLUSIONS: The clinical prediction model proposed in the ACCP guidelines showed unsatisfactory results in terms of the differential diagnosis between malignant disease and benign disease of solitary lung nodules in our study, because the specificity, negative predictive value and AUC were relatively low.

Postoperative bleeding after surgery in patients with lung cancer.

BACKGROUND: No reports regarding the risk factors for postoperative bleeding after surgery for lung cancer are available presently, and no practical management strategy has been yet developed. The purpose of this study was to determine the risk factors for postoperative bleeding requiring surgery, and we further discuss possible management strategies based on our findings. PATIENTS AND METHODS: Three hundred and sixteen patients with primary lung cancer underwent surgical resection, and we evaluated cases with postoperative bleeding. We examined the relationships between postoperative bleeding and clinicopathological characteristics. RESULTS: Postoperative bleeding requiring surgery occurred in four (1.3%) out of 316 patients. All four patients had a comorbid condition. No significant correlation was identified between postoperative bleeding and age, gender, smoking status, clinical stage, pathological stage or histology. The incidence of recurrence was higher in those with comorbidities among the bleeding cases. Concerning the intraoperative factors, there were no significant differences in the approach, lesion site, procedure or surgeon. CONCLUSION: The cases with postoperative bleeding had a tendency to have more comorbidities compared to non-bleeding cases. The current findings revealed that the handling of blood vessels might be related to the onset of postoperative bleeding.

Factors predicting the surgical outcome in patients with T3/4 lung cancer.

PURPOSE: Locally advanced lung cancer, such as T3/4 tumors, is considered to have a significantly worse prognosis than lower-stage disease, and the treatment of these tumors is difficult. Nevertheless, the information regarding the optimal treatment of T3/4 lung cancers after an operation is still limited. This study evaluated the prognostic factors for the postoperative outcome in patients with T3/4 lung cancers. METHODS: The results of the surgical treatments were retrospectively analyzed for 212 patients with pathological T3 and 197 patients with T4 disease. RESULTS: The global 5-year survival rate was 30.7% in this series. The 5-year overall survival (OS) rate in patients with T3 disease was 36.1%, while that in patients with T4 disease was 24.8%. The prognosis in females, those with N0-1 disease and those who underwent a complete resection was better than that of the other patients in both the T3 and T4 subgroups. The examination of the OS according to a time series showed that the rate was higher in more recent versus less recent years. From the standpoint of pulmonary metastasis (PM), the 5-year OS rates in T4 patients with PM and without PM were 38.6 and 17.4%, respectively. Multivariate analyses demonstrated that female gender, T3 disease, N0-1 disease and postoperative treatment were significant favorable prognostic predictors for OS. CONCLUSIONS: These findings suggest that surgical resection remains an important treatment option, especially in cases having the aforementioned factors.

Clinical significance of epithelial-mesenchymal transition-associated markers in malignant pleural mesothelioma.

Epithelioid tumors with aggressive behavior have been reported; however, the epithelioid type of malignant pleural mesothelioma (MPM) has a less aggressive behavior. Few studies have evaluated the prognostic value of epithelial-mesenchymal transition (EMT) markers in MPM. We hypothesized that mesenchymal characteristics might predominate in the tumors. Tumor specimens were collected from 33 consecutive patients. We analyzed the EMT expression levels in tumor samples by an immunohistochemical analysis. Positive expression of E-cadherin, γ-catenin, vimentin, fibronectin, Twist and YB-1 was observed in 25, 14, 21, 1, 19 and 18 patients, respectively. No significant association between these markers and the clinicopathological characteristics was found. γ-Catenin demonstrated a trend towards decreased expression in sarcomatoid tumors compared to epithelioid tumors. On the other hand, a trend was noted towards higher expression of vimentin, Twist and YB-1 in sarcomatoid tumors. The survival curves demonstrated that the patients with negative γ-catenin and positive Twist staining had a tendency to have a worse prognosis. Although the individual proteins might not significantly affect the progression of MPM, the combination of γ-catenin and Twist staining can predict the prognosis of patients with MPM.

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.

Discriminative features of thin-slice computed tomography for peripheral intrapulmonary lymph nodes.

BACKGROUND: The use of computed tomography (CT) scans has increased the opportunities to detect small nodular shadows in peripheral lung fields. Intrapulmonary lymph nodes (IPLNs) are sometimes identified among these nodular shadows, and a differential diagnosis is often difficult. However, few descriptions of the CT findings of IPLNs, with regard to their potential for the differential diagnosis of lung cancer, have been published. METHODS: From 2006 through 2011, 606 patients underwent thoracic surgery for pulmonary nodules. Nine patients (1.5%) had pathologically diagnosed IPLNs. We retrospectively reviewed the clinicopathological features and thin-section CT findings of the patients with IPLNs. We also compared these IPLN patients with 17 patients having small-sized lung cancer. RESULTS: In six cases, the nodules were round, and linear density extending from the IPLNs was visualized in seven nodules. The nodules in IPLNs were located in the lower lobe, and the nodule borders were clearer than those of lung cancers. Six out of nine nodules were round, and linear densities were more easily visualized for the IPLNs. CONCLUSION: Medical specialists need to be familiar with the discriminative features of thin-slice CT for IPLNs not only to avoid performing unnecessary operations, but also to prevent the mis-staging of lung cancer.

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.

What factors predict recurrence of a spontaneous pneumothorax?

BACKGROUND: The purpose of this retrospective study was to identify the risk factors for postoperative recurrence for the patients with a spontaneous pneumothorax (SP). A total of 214 patients were studied over a period of five years. Of these patients, 189 (88.3%) and 25 (11.7%) underwent video assisted thoracoscopic surgery (VATS) and an open approach for treatment, respectively. There were 35 (16.4%) postoperative recurrences. METHODS: The data on patient characteristics, surgical details, and perioperative outcomes were analyzed. We compared the clinicopathological characteristics between recurrent and non-recurrent cases, and used logistic regression models to predict the risk factors for postoperative recurrence. RESULTS: The differences in the age, gender, lesion site, location, ipsilateral SP (ISP), and contralateral SP (CSP) did not reach statistical significance between the two groups. However, the incidence of recurrence was higher in the subjects without any smoking history, and who had comorbidities, and a history of surgery for ISP. Concerning intraoperative factors, there were no significant differences with regard to the approach, buttress stapling, covering, surgeon, or length of the operation. The postoperative recurrence rate was higher in the patients who had been hand-stitched compared to those who had undergone instrument-based repair for blebs. There were no significant differences in the perioperative outcomes. The logistic regression models indicated that non smokers, those with comorbidities, and those who had previously undergone surgery for ISP had a higher rate of postoperative recurrence. CONCLUSIONS: We conclude that a history of no smoking, the existence of comorbidities, previous surgery for ISP, and hand stitching increase the risk of postoperative recurrence. Therefore, surgeons must be aware of these risk factors, and more carefully monitor such patients for recurrence.

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.