Kenro Takahashi

Prognostic significance of the size of central fibrosis in peripheral adenocarcinoma of the lung

BACKGROUND The prognostic significance of the characteristics of central fibrosis in peripheral adenocarcinoma of the lung has been reported. However, the prognostic significance of the size of central fibrosis has never been evaluated. METHODS A total of 100 consecutive surgically resected peripheral adenocarcinomas of the lung measuring 3.0 cm or less in maximum dimension were reviewed histologically, and the maximum dimension of central fibrosis was measured on conventional hematoxylin and eosin stain. RESULTS Median follow-up for patients alive was 54 months. The overall 5-year survival rate was 75%. Twenty-one patients with adenocarcinoma having central fibrosis 5 mm or smaller in maximum dimension had a 5-year survival rate of 100%, whereas the other 79 patients had a 5-year survival less than 70%. Multivariate analysis showed the size of central fibrosis to be an independent prognostic factor as significant as vascular invasion and locoregional lymph node metastasis (p = 0.010, 0.024, and 0.024, respectively). CONCLUSIONS The size of central fibrosis is an independent prognostic factor in peripheral lung adenocarcinoma, as significant as the well-established prognostic factors vascular invasion and lymph node metastasis.

Prevalence and specificity of LKB1 genetic alterations in lung cancers.

Germline LKB1 mutations cause Peutz–Jeghers syndrome, a hereditary disorder that predisposes to gastrointestinal hamartomatous polyposis and several types of malignant tumors. Somatic LKB1 alterations are rare in sporadic cancers, however, a few reports showed the presence of somatic alterations in a considerable fraction of lung cancers. To determine the prevalence and the specificity of LKB1 alterations in lung cancers, we examined a large number of lung cancer cell lines and lung adenocarcinoma (AdC) specimens for the alterations. LKB1 genetic alterations were frequently detected in the cell lines (21/70, 30%), especially in non-small cell lung cancers (NSCLCs) (20/51, 39%), and were significantly more frequent in cell lines with KRAS mutations. Point mutations were detected only in AdCs and large cell carcinomas, whereas homozygous deletions were detected in all histological types of lung cancer. Among lung AdC specimens, LKB1 mutations were found in seven (8%) of 91 male smokers but in none of 64 females and/or nonsmokers, and were significantly more frequent in poorly differentiated tumors. The difference in the frequency of LKB1 alterations between cell lines and tumor specimens was likely to be owing to masking of deletions by the contamination of noncancerous cells in the tumor specimens. These results indicate that somatic LKB1 genetic alterations preferentially occur in a subset of poorly differentiated lung AdCs that appear to correlate with smoking males.

Prognostic factors in clinical stage I non–small cell lung cancer

BACKGROUND Management of patients with early-stage lung cancer but a poor prognosis is controversial. METHODS Between January 1987 and December 1994, 365 patients with clinical stage I disease underwent surgical resection at our hospital. Eight preoperative clinical variables were entered into univariate and multivariate analyses to determine their impacts on 5-year survival. RESULTS The 3-year and 5-year survival rates were 78.1% and 66.5%, respectively. In the multivariate analysis, clinical T2 status and preoperative high serum carcinoembryonic antigen levels were independent significant factors indicative of a poor prognosis (hazard ratio, 2.20 and 1.88, respectively). Patients with both of these factors had 3-year and 5-year survival rates of 65% and 38% (p<0.001), and the risk of death for this subgroup was 4.14 times greater than that of the overall clinical stage I population. CONCLUSIONS A subgroup with clinical T2 disease and preoperative high serum carcinoembryonic antigen levels had a significantly poorer prognosis among patients with clinical stage I lung cancer. For this subgroup, a complete preoperative staging workup and multimodal therapy, especially induction chemotherapy, instead of surgical intervention alone could be beneficial.

The prognosis of surgically resected N2 non–small cell lung cancer: The importance of clinical N status

BACKGROUND Clinical trials dealing with multimodal strategy for N2 non-small cell lung cancer are now being watched with keen interest, and the feasibility of this strategy is to be confirmed. N2 lung cancer, however, is composed of several subgroups with different prognoses. The prognostic factors still remain controversial. METHODS Between January 1986 and July 1997, 222 patients with lung cancer underwent surgical intervention at our institute; these patients were eventually given a diagnosis of metastasis to ipsilateral mediastinal lymph nodes. All patients underwent mediastinal lymph node dissection or sampling. Sixteen clinicopathologic factors were investigated by univariable and multivariable analyses to identify significant prognostic factors among resected N2 disease. Clinical N status was evaluated by computed tomographic scan. RESULTS The overall 5-year survival was 27%. Multivariable analyses among overall patients revealed 4 significant prognostic factors (P <.05): clinical N2 status, incomplete resection, larger tumor size, and multiple diseased N2 nodes. Based on the result, 32 patients with both clinical N2 status and pathologic multiple N2 nodes showed a 5-year survival of 5%, whereas 76 patients with neither of the factors showed a 5-year survival of 57% (P <.001). CONCLUSION The prognosis of surgically resected N2 disease varies tremendously according to the 4 significant prognostic factors. These factors should be clearly described in reporting clinical trials on N2 lung cancer. Clinical N status evaluated by computed tomographic scan should be 1 criterion to perform a clinical trial for N2 disease among a homogeneous population with respect to prognosis.

Clinical predictors of N2 disease in the setting of a negative computed tomographic scan in patients with lung cancer

OBJECTIVES Although preoperative cervical mediastinoscopy is absolutely indicated for patients with lung cancer in whom computed tomography demonstrates mediastinal nodal enlargement, the indications when the computed tomographic scan is negative are controversial. To determine the indications in patients with negative computed tomographic scans, we retrospectively studied patients with surgically resected lung cancer. METHODS Between 1992 and 1997, 379 patients with lung cancer who had clinical N0-1 disease underwent surgical resection of lung cancer. Mediastinal lymph nodes were pathologically examined for metastasis in all the patients. A clinical diagnosis of nodal involvement was determined on the basis of preoperative computed tomographic findings: that is, mediastinal or hilar lymph nodes 1.0 cm or larger in the shortest axis were diagnosed as metastatic. Univariate and multivariate analyses were performed to determine the relationships between 9 clinical factors and pathologically proven N2 disease. RESULTS Among the patients with clinical N0-1 disease, 68 (17.9%) had pathologic N2 disease. Adenocarcinoma histology, large tumor dimension, and high serum carcinoembryonic antigen levels were significant predictors of pathologic N2 disease on the basis of multivariate analyses (P <.05). When these factors were combined, 43% of adenocarcinomas larger than 2.0 cm with high serum carcinoembryonic antigen levels (P <.001), 34.7% of adenocarcinomas with high serum carcinoembryonic antigen levels (P <.001), 25.6% of adenocarcinomas larger than 2.0 cm (P =.009), and 31.1% of patients with high serum carcinoembryonic antigen levels and large tumor dimension (P <.001) had pathologic N2 disease. CONCLUSION Preoperative cervical mediastinoscopy should be considered in patients in whom computed tomography is negative for lung cancer and who have some pathologic N2 predictive factors.

Clinicopathological characteristics of surgically resected lung cancer associated with idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is well known to be associated with lung cancer. It is important to clarify the clinical and pathological features of lung cancer with IPF in understanding the pathogenesis of lung cancer in IPF patients. We compared clinicopathological factors of lung cancer in patients with and without IPF.

Synchronous double primary lung carcinomas associated with multiple atypical adenomatous hyperplasia

A 71-year-old woman with synchronous bilateral primary lung carcinomas accompanied by multiple atypical adenomatous hyperplasias is described. The patient was found to have bilateral tumors during preoperative workup for the previously detected well differentiated adenocarcinoma of the right lung. Thoracoscopic wedge resection of the left upper lobe was performed to obtain a definitive diagnosis of the left lesion. Although intraoperative diagnosis was made by frozen section as atypical papillary lesion, postoperative diagnosis of this lesion was changed to well differentiated adenocarcinoma accompanied by surrounding atypical adenomatous hyperplasia (AAH). We diagnosed that the bilateral lesions were synchronous primary well differentiated adenocarcinomas independent to each other based on the criteria of Martini and Melamed and performed right upper and mediastinal lymph node dissection. The resected lobe contained not only the primary adenocarcinoma but also multiple small gray nodules which were diagnosed as AAHs. In summary, it was diagnosed that the patient had synchronous double primary lung adenocarcinomas of T1 N0 M0 pathological stage and 12 solitary atypical adenomatous hyperplasias. The patient is doing well with no signs of recurrence 24 months after the operation. This case might be an example of the adenoma-carcinoma sequence of lung cancer. A careful follow-up study is mandatory for this patient with special regard to the further development of lung carcinoma in the future.

Computed tomography-fluoroscopy guided injection of cyanoacrylate to mark a pulmonary nodule for thoracoscopic resection.

BACKGROUND There have been several reports regarding aids to localize small and/or deeply situated peripheral pulmonary lesions thoracoscopically. However, we have found that they were not always reliable and have attempted to use a cyanoacrylate adhesive as an alternative. METHOD We injected 0.1-0.2 ml of Histoacryl (n-butyl-2-cyanoacrylate) blue through a 22 gauge long needle to the lung parenchyma immediately beneath the pleural surface that was nearest to the target nodule. Following local anesthesia of the thoracic wall, we inserted the needle tip to the desired position under CT-fluoroscopic guidance. After retracting the syringe piston to confirm that no blood was aspirated, we injected the adhesive and immediately removed the needle. RESULTS The adhesive polymerized immediately after its injection into the lung parenchyma to form a hard nodule. There was no complication except mild pneumothorax and slight pain at the puncture site. The adhesive nodule measured 1.0-1.5 cm in diameter and was hard enough to be easily located thoracoscopically in all the 8 patients/9 nodules studied. The nodule was also recognizable by its blue color visible under the pleura. CONCLUSION CT-fluoroscopy guided injection of Histoacryl blue provided a reliable marker for the localization of pulmonary nodules, especially in those patients with severe anthracosis in the pulmonary parenchyma.

Postoperative mediastinal chyloma

Anterior mediastinal mass developed in a 69-year-old woman who had undergone right upper lobectomy and systematic lymph node dissection. The mass was diagnosed to be a mediastinal chyloma and surgical intervention was necessary to resolve the compression to the superior vena cava. Although posttraumatic mediastinal chyloma is not rare, postoperative mediastinal chyloma has not been reported in the literature. However, it should be noted as a differential diagnosis for a postoperative mediastinal mass.

Low-grade B-cell lymphoma of mucosa-associated lymphoid tissue in the lung: a report of a case with pleural dissemination

A 79-year-old man with an abnormal shadow on a chest radiograph was referred to our hospital for further examination. Open lung biopsy revealed numerous nodules on visceral pleura and the tumor, obtained by wedge resection of the left upper lobe of the lung, consisted of centrocyte-like cells and lymphoplasmacytoid cells, expressing CD20 and CD79a. These cells invaded bronchiolar epithelium to form lymphoepithelial lesions. The pleural-based nodules were similarly composed of the same cells as those in the left upper lobe tumor. To our knowledge, pleural dissemination of low grade B-cell lymphoma of mucosa-associated lymphoid tissue has not been reported previously.