Prognostic value of carcinoembryonic antigen and CYFRA21-1 in patients with pathological stage I non-small cell lung cancer.

BACKGROUND: The aim of this retrospective study was to assess the prognostic value of serum tumor markers (carcinoembryonic antigen (CEA) and CYFRA21-1) in patients with pathologic (p-) stage I non-small cell lung cancer (NSCLC) undergoing complete resection. METHODS: Two hundred and seventy-five patients (163 males, 112 females, mean age 67.1 years) with p-stage I NSCLC who underwent complete resection at our institution between April 1999 and October 2004 were examined. Patients who had received preoperative chemotherapy or radiotherapy were excluded, as were patients who had multiple malignancies including multiple lung cancer. The serum levels of tumor markers were measured using commercially available immunoassays within 1 month before surgical resection. Serum levels of CEA and CYFRA21-1 higher than 5.0 and 2.8 ng/ml, respectively, were considered as positive according to the manufacture's instructions. RESULTS: The histological classification was adenocarcinoma in 193 patients, squamous cell carcinoma in 71, large cell carcinoma in 5, and other histological type in 6. One hundred and fifty-seven patients had T1 disease and 118 patients had T2 disease. The positive ratio of CEA and CYFRA21-1 was 25.7% and 13.7%, respectively, and in relation to histological type was 27.8% and 7.8% in adenocarcinoma, and 20.6% and 28.4% in squamous cell carcinoma. The overall 5-year survival rate was 79.3%. With a median follow-up of 35.5 month for surviving patients, those with initial CYFRA21-1 serum levels higher than 2.8 ng/ml had a significantly worse prognosis (p=0.0041). Patients with an elevated preoperative CEA level exceeding 5.0 ng/ml had a shorter disease-free survival period (p=0.0003). In patients with adenocarcinoma, a CEA level above 5.0 ng/ml was associated with shorter survival and early recurrence, whereas CYFRA21-1 showed no such association. In patients with squamous cell carcinoma, elevated preoperative CEA was not related to survival and recurrence. In these patients, preoperative CYFRA21-1 level exceeding 2.8 ng/ml was associated with a poorer outcome, whereas preoperative CYFRA21-1 level was not associated with cancer recurrence. CONCLUSION: The patients with p-stage I adenocarcinoma whose preoperative CEA level was high might be considered as good candidates for adjuvant chemotherapy. The prognostic value of CYFRA21-1 could not be confirmed for stage I NSCLC, and preoperative CYFRA21-1 level was not useful in selecting the candidates for adjuvant chemotherapy.

A rare case of mediastinal functioning parathyroid adenoma removed successfully with thoracoscopy.

We report here a rare case of primary hyperparathyroidism that was associated with an ectopic parathyroid adenoma located in the mediastinum. A 66-year-old woman suffering from primary hyperparathyroidism had been followed-up on an outpatient basis for over 10 years. She suffered from persistent urolithiasis and osteopenia due to hypercalcemia. After technetium-99-sestamibi (99mTc-MIBI) scintigraphy revealed an ectopic adenoma in the superior mediastinum, thoracoscopic resection of the tumor was performed. Subsequently, her serum parathyroid hormone (PTH) level decreased dramatically and her serum calcium concentration was restored to normal. Two years following surgery, her serum PTH and Ca levels remain stable.

Ciliated muconodular papillary tumor of the lung: report of five cases.

We report five serial cases of ciliated muconodular papillary tumor (CMPT) of the lung. CMPT is characterized as a low-grade malignant tumor with ciliated columnar epithelial cells combined with goblet cells, typically presenting as peripheral lung tumor and often causing diagnostic or therapeutic problems. In the cases described here, all patients presented with abnormal chest shadow but no definitive symptoms. Although all tumors were peripheral, computed tomography (CT) revealed various radiographic findings including small lung nodules, ground-grass opacity or irregular-shaped consolidation. All patients underwent complete surgical resection, and no recurrence has been noted over follow-up. In all cases, pathological findings included columnar ciliated cells with mucus lakes, consistent with the immunohistochemical staining. As there are few reports on this tumor entity, which has not yet received a WHO classification, we believe our case series may be of interest.

Survivin gene expression is negatively regulated by the p53 tumor suppressor gene in non-small cell lung cancer.

Survivin is considered to be associated with tumorigenesis by regulating apoptosis and cell proliferation. Recent experimental studies reported survivin gene expression to be negatively regulated by wild-type p53. We investigated resected tumor specimens from 140 non-small cell lung cancer (NSCLC) patients. Quantitative reverse-transcription PCR analysis was performed to evaluate survivin gene expression. PCR-single strand conformation polymorphism following sequencing was performed to investigate mutations of p53. The apoptotic index and the Ki-67 proliferation index were also evaluated according to the survivin expression. The survivin expression was low in normal lung tissue. In contrast, the survivin expression varied greatly among tumor tissues. The survivin expression in squamous cell carcinomas was significantly higher than that in adenocarcinomas (P=0.0109). The survivin expression in moderately or poorly differentiated tumors was significantly higher than that in well-differentiated tumors (P=0.0334). Furthermore, the survivin expression in tumors with mutant p53 was significantly higher than that in tumors with wild-type p53 (P=0.0026). In addition, the apoptotic index was significantly lower in high-survivin tumors than in low-survivin tumors (P<0.0001). The Ki-67 proliferation index was significantly higher in high-survivin tumors than in low-survivin tumors (P<0.0047). This study indicated survivin gene expression to be negatively regulated by p53 in NSCLC, and that survivin expression could inhibit apoptosis and accelerate tumor cell proliferation to produce more aggressive carcinomas.

Reduced ING1b gene expression plays an important role in carcinogenesis of non-small cell lung cancer patients.

PURPOSE: We performed a clinical study on ING1b gene expression and p53 gene status in relation to p53 target genes. EXPERIMENTAL DESIGN: Eighty-eight tumors from surgically treated non-small cell lung cancer (NSCLC) patients were studied. PCR-single-strand conformational polymorphism after sequencing was performed to investigate ING1 and p53 gene status. Quantitative reverse transcription-PCR was performed to evaluate the gene expression of ING1b, p21, and bax. The results of p21 and bax expression were confirmed with immunohistochemistry. RESULTS: Only two carcinomas (2.3%) had nonmissense mutations of ING1b. Thirty-seven carcinomas (42.0%) had reduced ING1b gene expression. Thirty-seven carcinomas (42.0%) had mutations of p53. In total, 63 carcinomas (71.6%) had either reduced ING1b expression or mutant p53. The p21 gene expression ratio was significantly lower in the ING1b-reduced tumors than in the ING1b-positive tumors (P = 0.0029). Similarly, the bax gene expression ratio was significantly lower in the ING1b-reduced tumors than in the ING1b-positive tumors (P < 0.0001), and it was also significantly lower in tumors that had either reduced ING1b expression or mutant p53 than in tumors that had both positive ING1b expression and wild-type p53 (P = 0.0331). CONCLUSIONS: Reduction of ING1b gene expression was associated with reduced p21 and bax gene expression in NSCLCs. The present study is the first clinical report to confirm the positive role of ING1b in regulating p21 and bax gene expression. ING1b might be one of the tumor suppressor genes that could play a role in carcinogenesis in NSCLC patients.

Prognostic factors after complete resection of pN2 non-small cell lung cancer.

OBJECTIVES: This retrospective, multicenter study aimed to determine prognostic factors of completely resected pathologic N2 stage IIIA non-small cell cancer (NSCLC). METHODS: From 25 participating hospitals, 496 patients (325 men and 171 women; median age, 65 years) who underwent complete resection without preoperative treatment for pT1-3 N2 M0, stage IIIA NSCLC between 2000 and 2004 were enrolled. Lobectomy/bilobectomy was performed in 462 patients and pneumonectomy in 34. Some kind of adjuvant chemotherapy was administered to 296 patients. Survivals were calculated using the Kaplan-Meier method, and prognostic factors were determined using the Cox proportional hazards model. RESULTS: Five-year overall survival (OS) and disease-free survival (DFS) were 44.8% and 24.2%, respectively. pT classification (hazard ratio (HR), pT1/pT2/pT3 = 1/1.32/2.03), single or multiple N2 metastases (HR, single/multiple = 1/1.36), and skip or nonskip N2 metastasis (HR, skip/nonskip = 1/1.30) were found to be independent prognostic factors for DFS. Sex (HR, female/male = 1/1.36), performance status (HR, PS-0/PS-1 = 1/1.37), tumor diameter (HR, 1.12 per 1-cm increase), pT-factor (HR, pT1/pT2/pT3 = 1/1.37/2.22), and extent of N2 metastasis (HR, localized/extended = 1/1.39) were shown to be independent prognostic factors for OS. CONCLUSIONS: We found that pT classification was a significant prognostic indicator for OS and DFS whereas tumor diameter, performance status, and sex were ones for OS. Single N2 metastasis and skip N2 metastasis were demonstrated as favorable prognostic factors for DFS, limited N2 metastasis was one for OS, and these should be considered as stratification factors for trial on adjuvant therapy.

Preoperative hypoalbuminemia is a risk factor for late bronchopleural fistula after pneumonectomy.

BACKGROUND: Pneumonectomy is still a high-risk surgical procedure. Postpneumonectomy bronchopleural fistula is an especially severe complication with a high mortality rate. Although several reports have discussed risk factors for early bronchopleural fistula after pneumonectomy, only a few have reported them for late bronchopleural fistula. We reviewed cases of late bronchopleural fistula after pneumonectomy and investigated its risk factors. METHODS: Sixty-four patients with nonsmall cell lung cancer underwent pneumonectomy at our institution from June 1999 to December 2004. Among them, 5 who developed bronchopleural fistula were investigated. RESULTS: All of the 5 patients were male; 3 had undergone right pneumonectomy and 2 left pneumonectomy. The period between surgery and the appearance of bronchopleural fistula ranged from 36 to 164 days. We found that the preoperative serum albumin level was significantly lower in the patients with late bronchopleural fistula. Induction therapy, surgical side, age, anemia, arterial blood oxygen, and respiratory function did not affect the occurrence of bronchopleural fistula after pneumonectomy. CONCLUSIONS: A preoperative low-serum albumin level, indicative of poor nutritional status, is a risk factor for late bronchopleural fistula after pneumonectomy for nonsmall cell lung cancer.

Prognostic factors in patients with pathologic T1-2N1M0 disease in non-small cell carcinoma of the lung.

INTRODUCTION: Patients with stage II non-small cell lung carcinoma (NSCLC) represent a heterogeneous subgroup with variable 5-year survival rates. The influence of the type of lymph node involvement on survival and recurrence was investigated. METHODS: A total of 128 consecutive patients who underwent complete tumor resection and mediastinal lymph nodes dissection for pT1-2N1M0 NSCLC between July 1991 and December 2003 were retrospectively reviewed. RESULTS: The overall 5-year survival of patients with T1-2N1M0 disease was 42.2%. Although pT status, histology, surgical procedure, and adjuvant therapy did not affect survival for pT1-2N1M0 patients, the 5-year survival rate differed significantly according to the type of lymph node involvement. The 5-year survival rate for patients with main bronchial lymph node involvement, interlobar and lobar lymph node involvement, and segmental bronchial lymph node involvement was 19.7%, 39.8%, and 59.7%, respectively. The survival curves of these three groups had significant differences. Fifty-five patients had cancer recurrence, and the type of lymph node involvement did not affect the pattern of cancer relapse. CONCLUSIONS: In patients with stage II NSCLC, survival differs according to the type of lymph node involvement: patients with only segmental lymph node involvement have a better prognosis and the disease seems to be at an early stage, whereas patients with main bronchial lymph node involvement have a poorer prognosis, and main bronchial lymph node involvement represents more advanced disease. Patients with pN1 disease represent a heterogeneous group that may be subdivided according to the level of the involved N1 station, not pT factor.

Pulmonary cavernous hemangioma.

We report a rare case of pulmonary cavernous hemangioma in a 54-year-old man. A computed tomographic scan of the chest showed an ill-defined mass measuring 4 x 3 cm at the angle of the left upper lobe bronchus and the lower lobe bronchus. Surgical resection was performed to obtain a definitive diagnosis. Postoperative histological examination revealed an encapsulated mass comprising large dilated vessels lined with squamous endothelium and filled with blood, which led to the diagnosis of pulmonary cavernous hemangioma. A total of 23 cases including the present case reported in the English-language and Japanese literature were reviewed.

Topoisomerase IIalpha gene expression is regulated by the p53 tumor suppressor gene in nonsmall cell lung carcinoma patients.

BACKGROUND: Topoisomerase IIalpha (Topo IIalpha) is an essential nuclear enzyme for chromosome segregation during mitosis. Previous experimental studies using cell lines reported that Topo IIalpha expression was negatively regulated by wild-type p53 through the gene's promoter region. METHODS: Surgically resected tumor specimens from 98 nonsmall cell lung carcinoma (NSCLC) patients who were not treated with preoperative chemotherapy were studied. Quantitative reverse-transcription polymerase chain reaction analysis was done to evaluate Topo IIalpha gene expression. Polymerase chain reaction single strand conformation polymorphism following sequencing was performed to investigate mutations of p53. RESULTS: Topo IIalpha gene expression in squamous cell carcinomas was significantly higher than in adenocarcinomas (P = 0.0007). Topo IIalpha gene expression in moderately differentiated tumors and poorly differentiated tumors was significantly higher than in well differentiated tumors (P = 0.0032 and P = 0.0005, respectively). Thirty nine tumors (40%) had mutations of p53. Topo IIalpha gene expression in tumors with mutant p53 was significantly higher than in those with wild-type p53 (P = 0.0224). CONCLUSIONS: The current study suggests that Topo IIalpha gene expression is regulated by p53 gene status in NSCLC patients and that the overexpression of Topo IIalpha induced by mutant p53 might cause more aggressive carcinogenesis.