Surgical outcomes of pulmonary metastases from esophageal carcinoma diagnosed by both pathological and clinical criteria.

PURPOSE: This investigation was performed to examine the surgical outcomes of pulmonary metastases from esophageal carcinoma (EC) diagnosed by both pathological and clinical criteria. METHODS: Based on the pathological criteria, we identified 22 patients who had undergone pulmonary metastasectomy for EC between 1997 and 2011. Thehistological type of EC was squamous cell carcinoma (SCC) in all patients. After specific clinical criteria were applied, seven patients suspected of having primary lung SCC were excluded. The surgical outcomes of the remaining 15 patients were reviewed. The overall survival (OS) was calculated as the period from pulmonary resection until death or the date of the last follow-up. RESULTS: The 1-, 3- and 4-year OS rates of the 15 patients were 93, 44 and 0% respectively, with a median OS of 32 months. A larger diameter of the pulmonary metastasis was marginally associated with a poorer OS (p = 0.087); however, none of the parameters were significant prognostic factors. CONCLUSIONS: The median OS of patients who underwent surgical resection for pulmonary metastases from EC was comparable to that in previous reports, even after excluding patients clinically suspected of having a second primary lung SCC. The poor long-term survival might indicate that our clinical criteria are helpful in selecting true metastatic patients, considering the aggressive clinical course of metastatic EC.

Results of surgical treatment for non-small cell lung cancer with positive sputum cytology: experience from a single institution.

BACKGROUND: Little is known about the prognostic value of positive sputum cytology in patients with non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: We retrospectively examined the clinicopathological data of 30 patients who had undergone complete resection for NSCLC with positive sputum cytology between September 2002 and June 2011. RESULTS: Distant recurrence occurred significantly more frequently in the patients with adenocarcinoma (Ad) than in those with squamous cell carcinoma (p = 0.01). The most frequent metastatic site after surgery was the brain, occurring in five patients with Ad. The 5-year disease-free survival (DFS) and overall survival (OS) rates of the 30 patients were 53 and 49%, respectively. In multivariate analyses, radiographic feature of pneumonic-type shadow and pathological N (pN) 1-2 status were the independent factors significantly correlated with poor DFS (p = 0.009, 0.001, respectively), whereas pN 1-2 status was the only independent factor significantly correlated with poor OS (p = 0.009). CONCLUSION: Surgical outcome for NSCLC with positive sputum cytology was unfavorable at our institution. Close surveillance after a curative resection is mandatory for those patients presenting with radiographic feature of pneumonic-type shadow as those with lymph node metastases because they are at high risk for recurrence.

[Pulmonary metastases from colon cancer and occult thyroid cancer in the same lobe].

A 70-year-old man with a history of surgery for colon cancer was found to have multiple enlarging pulmonary nodules( 2 in the left lower lobe and 1 in the right upper lobe), and was suspected of having pulmonary metastases from colon cancer. He underwent left lower lobectomy, and subsequent histopathological examination revealed that one was a pulmonary metastasis from colon cancer, and the other was a pulmonary metastasis from papillary thyroid cancer. There were no abnormalities in the thyroid gland according to computed tomography and ultrasonography findings. Therefore, the patient was diagnosed with synchronous pulmonary metastases of both colon cancer and occult thyroid cancer in the same lobe. This is an exceedingly rare case;to the best of our knowledge, there has been no report thus far regarding multiple pulmonary metastases from different primary sites.

Long-term survival after superior vena cava resection and reconstruction for bulky local recurrence from lung cancer.

A 65-year old man who had undergone right pneumonectomy for lung cancer presented with superior vena cava (SVC) syndrome due to recurrent bulky disease on follow-up after 14 months. Complete resection of the tumour was achieved, and the SVC system was reconstructed with separated double grafts. The right graft was anastomosed between the SVC and the right subclavian vein, because the right brachiocephalic vein was involved by the tumour. Graft-subclavian vein anastomosis was created in the extra-thoracic portion. Although postoperative right graft occlusion occurred, right arm oedema improved conservatively. He is alive, well and has been disease-free for 39 months since the second surgery. This is the first report of SVC resection and reconstruction for 'recurrent' disease from lung cancer. Extended resection for recurrent disease should not be excluded as a treatment option.

A solitary mixed squamous cell and glandular papilloma of the lung.

Mixed squamous cell and glandular papilloma (mixed papilloma) of the lung is exceedingly rare, with only 18 cases reported in the literature. Herein, we report a case of mixed papilloma and its associated immunohistochemical and positron emission tomographic (PET) findings. A 60-year-old Japanese male with a smoking history of 40 pack-years presented with a smooth-edged pulmonary lesion in the right S5 segment on computed tomography (CT). F18-fluorodeoxyglucose (FDG) PET revealed abnormally increased FDG uptake in the mass (maximum standardized uptake value, 3.4). We performed right middle lobectomy and combined partial resection of the S8 segment. The 1.8-cm tumor that filled the enlarged lumen of the B5b was histologically diagnosed as mixed papilloma. Immunohistochemically, the pseudostratified columnar epithelium was positive for cytokeratin (CK) 5/6 and CK7. p40 positivity was predominant in the basal and squamous cells. Thyroid transcription factor-1 and carcinoembryonic antigen were negative on immunostaining. Malignant features were absent. The postoperative course has been uneventful for 3 months after the surgery. No recurrences were reported after the surgical resection of the mixed papilloma. Therefore, surgical resection may be considered the mainstay of curative treatment.

Epithelioid inflammatory myofibroblastic sarcoma arising in the pleural cavity.

A 57-year-old Japanese man presented with massive right pleural effusion, and a huge tumor arising in the pleural cavity was detected by chest computed tomography. A thoracoscopic tumor biopsy revealed that the tumor protruded extensively into the pleural cavity, and its gross appearance was cystic and glossy. Microscopically, the tumor cells were rounded and epithelioid in shape. Prominent and abundant myxoid stroma was also present together with an inflammatory infiltrate, and the tumor was anaplastic lymphoma kinase (ALK)-immunopositive. Fluorescence in situ hybridization revealed that the Ran-binding protein 2-ALK fusion gene was present. Taken together, these findings supported the diagnosis of epithelioid inflammatory myofibroblastic sarcoma (EIMS), which is a variant of an inflammatory myofibrobrastic tumor. This is the first reported case of an EIMS arising in the pleural cavity.

Single institutional experience with primary mediastinal cysts: clinicopathological study of 108 resected cases.

PURPOSE: To review our institutional surgical outcomes with primary mediastinal cysts (PMCs) and elucidate the clinicopathological differences among several histological PMC variants. METHODS: We retrospectively reviewed 108 patients who underwent surgery for PMC at our institution between 1997 and 2012. RESULTS: There were 54 thymic cysts (TCs), 26 bronchogenic cysts (BCs), 16 mature cystic teratomas (MCTs), 11 pericardial cysts (PCs), and 1 esophageal duplication cyst. Surgical approach was via thoracoscopy in 44, thoracotomy in 24, median sternotomy in 39, and hemiclamshell incision in 1. Pathological complete resection was achieved in all patients. Postoperative complications occurred in 13 patients. There was no postoperative mortality. All patients were recurrence-free after a mean follow up of 41 ± 26 months. MCT was significantly associated with larger cyst size (p <0.001) more frequent combined resection of invaded organs (p <0.001), more intraoperative bleeding (p = 0.005), and longer duration of operation (p = 0.022) than the 3 other groups (TC, BC, and PC). CONCLUSION: Surgical treatment for PMC is safe and efficacious regardless of approach. Patients with MCT may require more aggressive surgeries than those with other histological variants, reflecting their potential for invasion into surrounding structures and larger cyst size.

Aggressive adenocarcinoma of the lung consisting solely of discohesive cells.

A 60-year-old Japanese man was found to have diffuse pneumonia-like shadow in the left S10 segment on chest computed tomographic scan. Transbronchial lung biopsy yielded a pathological diagnosis of poorly differentiated adenocarcinoma; subsequently, left lower lobectomy was performed. Histopathological analysis showed that the tumor consisted solely of discohesive cells with involvement of the hilar and mediastinal lymph nodes. The immunohistochemical expression of E-cadherin and ß-catenin was low, whereas that of p53 was high in the tumor cells. Here, we describe a rare lung adenocarcinoma with discohesive cells, which are considered to indicate high tumor aggressiveness.

Risk factors for both recurrence and survival in patients with pathological stage I non-small-cell lung cancer.

OBJECTIVES: Even after curative resection, a significant fraction of patients with stage I non-small-cell lung cancer (NSCLC) die primarily because of systemic relapse. The purpose of the present study was to investigate the risk factors for both recurrence and poor survival in patients with pathological (p-) stage I NSCLC. METHODS: We retrospectively reviewed 467 consecutive patients from a single institution with completely resected p-stage I NSCLC. Patients with multiple lung tumours or malignancies from other organs and those who had undergone preoperative therapies were excluded. The correlation between clinicopathological factors and surgical outcomes, including disease-free survival (DFS) and overall survival (OS), was analysed. The clinicopathological factors examined were age, gender, smoking history, serum carcinoembryonic antigen (CEA) levels, serum cytokeratin 19 fragment levels, surgical procedure, tumour histology, p-stage, angiolymphatic invasion and differentiation grade. RESULTS: The 5-year DFS and OS rates of the total study population were 91.4 and 92.8%, respectively. Multivariate analysis results indicated that high serum CEA levels (>5.0 ng/ml) and p-stage IB were independent factors for recurrence, whereas older age (>70 years), high serum CEA levels and p-stage IB were independent factors for poor survival. The risks of recurrence and death in patients with both high serum CEA levels and p-stage IB was 10.3 and 5.2 times higher than those observed in patients with both normal serum CEA levels and p-stage IA, respectively. CONCLUSIONS: High serum CEA levels and p-stage IB were independent factors for both recurrence and poor survival in p-stage I NSCLC patients.

Prognostic significance of postoperative serum carcinoembryonic antigen levels in patients with completely resected pathological-stage I non-small cell lung cancer.

BACKGROUND: Until date, there are no clear recommendations for regular perioperative measurements of serum CEA levels for lung cancer in any guidelines. The purpose in the present study is to evaluate the prognostic significance of perioperative serum carcinoembryonic antigen (CEA) levels in patients with pathological-stage I non-small cell lung cancer (NSCLC). METHODS: We retrospectively reviewed 263 completely resected pathological-stage I NSCLC patients whose preoperative and postoperative serum CEA levels were measured. Patients were subdivided according to the perioperative change of CEA levels: continuously normal CEA levels (NN group), continuously high CEA levels (HH group), and high preoperative CEA levels that returned to normal levels post-operation (HN group). The clinicopathological factors and overall survival (OS) among these 3 groups were compared. Univariate and multivariate analyses of the correlation between clinicopathological factors and OS were performed. RESULTS: High preoperative CEA levels significantly correlated with men aged >70 years with smoking history, high serum CYFRA 21-1 levels, greater tumor diameter, presence of visceral pleural invasion (VPI), and moderate-to-poor differentiation. Five-year OS rates in the NN and HH groups were 95.5% and 59.3%, respectively. Four-year OS rate in the HN group was 85.5%. Multivariate analyses indicated tumor diameter of more than 30 mm, presence of VPI, and the HH group were independent unfavorable prognostic factors. CONCLUSIONS: A high postoperative CEA level was an independent unfavorable prognostic factor in pathological-stage I NSCLC patients. Patients with high postoperative CEA levels may benefit from adjuvant chemotherapy.

c-MET/phospho-MET protein expression and MET gene copy number in non-small cell lung carcinomas.

INTRODUCTION: The hepatocyte growth factor/MET pathway has been shown to cause tumor progression in several types of carcinomas. The aim of this study was to examine the correlations between c-MET/phospho-MET expression as well as MET gene copy number alterations and overall survival (OS) in non-small cell lung carcinomas (NSCLCs). METHODS: We analyzed 906 NSCLCs including 704 adenocarcinomas (ADCs), 150 squamous cell carcinomas (SCCs), 43 sarcomatoid carcinomas, and 9 large cell carcinomas. The mutational status of epidermal growth factor receptor and K-ras and anaplastic lymphoma kinase rearrangements were retrospectively examined. We performed immunohistochemistry to detect c-MET/phospho-MET expression and MET gene copy number using bright-field in situ hybridization (BISH). RESULTS: c-MET/phospho-MET expression and MET BISH positivity were observed in 22.2%, 5.6%, and 10.9% of NSCLCs, respectively; they were more prevalent in ADCs (27.3%, 6.9%, and 11.5%, respectively) and sarcomatoid carcinomas (20.9%, 9.3%, and 36.6%, respectively) than in SCCs and large cell carcinomas. Among ADCs, poorly differentiated cases exhibited c-MET expression and MET BISH positivity more commonly than well-differentiated ones. An analysis of all patients revealed that c-MET/phospho-MET expression and MET BISH positivity were not correlated with OS. However, when SCC cases were excluded, both univariate (p=0.019) and multivariate (p=0.020) analyses revealed a significant correlation between MET BISH positivity and OS. CONCLUSIONS: c-MET/phospho-MET expression and MET BISH positivity differed according to histological type. Among ADCs, c-MET expression and MET BISH positivity were more common in poorly differentiated cases. MET BISH positivity was an independent prognostic factor in nonsquamous NSCLCs.

Surgical treatment for pulmonary metastases from esophageal carcinoma after definitive chemoradiotherapy: experience from a single institution.

BACKGROUND: Surgical treatment for pulmonary metastases is known to be a safe and potentially curative procedure for various primary malignancies. However, there are few reports regarding the prognostic role of surgical treatment for pulmonary metastases from esophageal carcinoma, especially after definitive chemoradiotherapy (CRT). METHODS: We retrospectively reviewed 5 patients who underwent surgical treatment for pulmonary metastases from esophageal carcinoma at our institution. The primary treatment for esophageal carcinoma was definitive CRT, and a complete response (CR) was achieved in all patients. RESULTS: The surgical procedure for pulmonary metastases was wedge resection, and pathological complete resection was achieved in all 5 patients. The disease free interval after definitive CRT varied from 7 to 36 months, with a median of 19 months. There were no perioperative complications, but postoperative respiratory failure occurred in 1 patient. The postoperative hospital stay varied from 4 to 7 days, with a median of 6 days. Three patients are now alive with a good performance status (PS) and are disease free. The other 2 patients died of primary disease. The overall survival after surgical treatment varied from 20 to 90 months, with a median of 29 months. CONCLUSIONS: Surgical treatment should be considered for patients with pulmonary metastases from esophageal carcinoma who previously received CRT and achieved a CR, because it provides not only a longer survival, but also a good postoperative PS for some patients.

The usefulness of mutation-specific antibodies in detecting epidermal growth factor receptor mutations and in predicting response to tyrosine kinase inhibitor therapy in lung adenocarcinoma.

INTRODUCTION: Among the mutations of epidermal growth factor receptor (EGFR), deletions in exon 19 (DEL), and point mutations in exon 21 (L858R) predict the response to EGFR-tyrosine kinase inhibitors (TKIs) in primary lung adenocarcinoma. The ability to detecting such mutations using immunohistochemistry (IHC) would be advantageous. METHODS: The molecular-based and IHC-based EGFR mutations were analyzed in 577 lung adenocarcinomas using high resolution melting analysis (HRMA) and 2 mutation-specific antibodies, respectively. RESULTS: In the molecular-based analyses, DEL was detected in 135 cases (23%), and L858R was detected in 172 cases (30%). In the IHC-based analyses, a positive reaction was detected in 59 cases (10%) for the DEL-specific antibody, and in 139 cases (24%) for the L858R-specific antibody. With the molecular-based results set as the gold standard, the sensitivity and specificity of the DEL-specific antibody were 42.2% and 99.5%, respectively, while the sensitivity and specificity of the L858R-specific antibody were 75.6% and 97.8%, respectively. The antibody specificities improved when the threshold for the mutation-positive reactions was set as >50% of immunopositive tumor cells. The significant predictors of the clinical response to EGFR-TKI were molecular-based EGFR mutations (p<0.001) and IHC-based EGFR mutations (p=0.001). However, a multivariate analysis revealed that only molecular-based EGFR mutations were significantly correlated with the clinical response (p<0.001). CONCLUSIONS: Mutation-specific antibodies demonstrated extremely high specificities, but their sensitivities were not higher than those of molecular-based analyses. However, IHC should be performed before a molecular-based analysis, because it is more cost-effective and can effectively select candidates for EGFR-TKI therapy.