Hideoki Yokouchi

Intentional limited resection for selected patients with T1 N0 M0 non-small-cell lung cancer: A single-institution study

OBJECTIVES To comparatively evaluate lobectomy and limited resection for T1 N0 M0 non-small-cell lung cancer, we reviewed case series with concurrent nonrandomized controls. METHODS Limited resection with curative intent was performed for 63 patients with T1 N0 M0 non-small-cell lung cancer over a 10-year period. These 63 patients included 46 patients who underwent a segmentectomy as an intentional limited resection. These patients had good pulmonary function and could tolerate a lobectomy in the management of their disease. The other 17 patients underwent wedge resection or segmentectomy as a compromised limited resection because they had poor pulmonary reserve or other limiting factors and could withstand a thoracotomy but could not tolerate a lobectomy in the management of their disease. RESULTS The 5-year survival was 93% in the intentional resection group. The survival curve for this group was not different from that for 77 patients who underwent the standard operation (lobectomy plus complete mediastinal lymph node dissection) for T1 N0 M0 non-small-cell lung cancer during the same period. The frequency of local/regional recurrence in the intentional resection group was 8.7% (4/46); the recurrence in three patients was situated in the mediastinum. According to multivariate analysis, limited resection was not associated with poor survival. CONCLUSION Segmentectomy with regional lymph node dissection, including the mediastinum, should be considered as an acceptable alternative treatment for selected patients with T1 N0 M0 disease.

Prognostic value of ground-glass opacity found in small lung adenocarcinoma on high-resolution CT scanning

OBJECTIVE This study was undertaken to investigate the value of the ground-glass opacity (GGO) area found on high-resolution computed tomography (HRCT) scanning as a preoperative prognostic indicator. PATIENTS AND METHODS We studied 104 patients with small-sized lung adenocarcinoma, 20 mm or less in diameter, between 1995 and 1999. Three independent radiologists semi-quantitatively scored the extent of GGO on HRCT as greater than or less than 50%. Three independent pathologists semi-quantitatively scored the extent of the bronchioloalveolar carcinoma (BAC) component of the tumor on histologic examination as greater than or less than 50%. As no relapse occurred in patients with GGO greater than 50%, multivariate analysis of this prognostic factor was not possible. RESULTS Fifty patients were scored as having both BAC and GGO greater than 50%, 36 as both BAC and GGO less than 50%, and 16 as BAC greater than 50% and GGO less than 50%. In only two patients (1.9%), BAC less than 50% was overestimated on HRCT as GGO greater than 50%. The sensitivity and specificity of GGO to BAC were 76 and 95%, respectively. The 3 year-relapse-free survival rates in each group of 52 patients with GGO greater than and less than 50% were 100 and 72%, respectively, after a median follow-up of 24 months. Univariate analysis indicated that both GGO and BAC areas were significantly correlated with cancer relapse (P=0.005 and P=0.002). The multivariate analysis revealed an independent prognostic influence of the BAC area on relapse-free survival (P=0.015, relative risk=0.07). CONCLUSIONS To date there has been no relapse among the 52 patients with GGO greater than 50%. This novel classification based on the semiquantitative analysis of GGO area on HRCT should become an useful independent preoperative indicator when deciding on operative procedure, and to predict the potential of relapse in patients with small adenocarcinoma arising from the peripheral lung.

Natural history of pure ground-glass opacity after long-term follow-up of more than 2 years

BACKGROUND Pure ground-glass opacity (PGGO) is a new entity that has been clearly defined on high-resolution computed tomography (CT) during the last half decade. It is important to investigate the natural history of PGGO through long-term observation for the management of this new entity. METHODS We investigated 19 patients with PGGO(s) defined on high-resolution computed tomography and retained as PGGO for more than 2 years. The PGGOs of 11 patients were detected at annual mass screening by low-radiation-dose CT (low-dose CT), 7 at follow-up CT after cancer resection, and 1 incidentally on CT. After long-term observation, 10 of 19 patients underwent operation and 9 are currently being followed-up with CT. Their growth characteristics and histologic findings are reported. RESULTS The median follow-up period was 32 months, ranging from 24 to 124 months. The sizes of PGGOs at the time of discovery were 4 to 18 mm in largest diameter (average 8.6 mm). During follow-up, the size of PGGO showed no change in 8 patients, increased slightly (up to 5 mm) in 6 patients, and increased by more than 5 mm in 5 patients. Ten patients had limited resection (segmentectomy or wide wedge resection) with negative surgical margin by intraoperative lavage cytology of the resection margin of the lung. Of them, 5 patients had adenocarcinoma, 3 pulmonary lymphoproliferative disorder, and 1 each atypical adenomatous hyperplasia and focal fibrosis. There was no clear tendency between the degree of size change and histology. In all but 1 of 9 patients with follow-up only, the PGGOs showed either no change or only a slight increase within 5 mm in largest diameter. CONCLUSIONS These data suggest that some PGGOs will never progress to clinical disease and would be included in the category of overdiagnosis bias. However, a prior history of lung cancer should significantly raise the index of suspicion, as 4 of 5 proven cancer cases in this small series fell into that category. Because of the difficulties of preoperative and intraoperative histodiagnosis of PGGO, minimally invasive surgery may be appropriate from the viewpoints of both diagnosis and curability.

Prognostic value of bronchiolo-alveolar carcinoma component of small lung adenocarcinoma

BACKGROUND Bronchiolo-alveolar carcinoma (BAC) is often observed in lung adenocarcinoma, but its clinicopathological and prognostic significance, especially in small peripheral lung adenocarcinoma, remains undetermined. METHODS We assessed 206 consecutive cases of surgically resected small peripheral lung adenocarcinoma (less than 2 cm in diameter) recorded between 1973 and 1997. According to the component area of well differentiated BAC within maximally cut surface specimens of tumor tissue, we semiquantitatively classified the tumors into four types: those in which the BAC component comprised 0% (type I), 1% to 49% (type II), 50% to 99% (type III), and 100% (type IV) of the tumor tissue. RESULTS Forty tumors were classified as type I, 75 as type II, 74 as type III, and 17 as type IV. The tumors with less BAC, especially type I and II, showed a significantly more aggressive nodal involvement and tumor stage, and consequently a worse prognosis, while type IV tumors had no nodal involvement and the most favorable prognosis. The patients with type III showed clinicopathological characteristics somewhere between those of type II and type IV patients. Among stage I patients, however, those with type II had the worst prognosis, while those with type I showed as good a prognosis as the other two groups. CONCLUSIONS This novel classification based on the degree of BAC involvement in small peripheral lung adenocarcinoma may reflect clinicopathological and prognostic characteristics. This classification may prove practical for planning therapeutic strategies, in particular surgical treatment.

Fibroadenoma and Phyllodes Tumor

Background. The histogeneses of fibroadenoma and phyllodes tumor of the breast appear to be closely related, but it is still unclear whether fibroadenoma can progress directly to phyllodes tumor.

Immunohistochemically detected expression of motility-related protein-1 (MRP-1/CD9) in lung adenocarcinoma and its relation to prognosis.

Motility‐related protein‐1 (MRP‐1)/CD9 is a trans‐membrane glycoprotein closely associated with suppression of cell motility and reduced metastatic potential of some tumor cells. We currently report that, according to the RT‐PCR method for MRP‐1/CD9 gene expression, patients with low expression of MRP‐1/CD9 in non‐small‐cell lung cancer, especially the adenocarcinoma type, showed short overall survival. Then, to determine accurately the prognostic value of MRP‐1/CD9 product levels in lung‐adenocarcinoma cells, we immunohistochemically investigated its expression in 132 lung‐adenocarcinoma patients undergoing potentially curative surgery. Of these patients, 44 (33%) showed reduced expression of MRP‐1/CD9 in cancer cells, and an inverse association was observed between its expression and factors associated with tumor progression, such as nodal involvement (p = 0.029) or stage (p = 0.028). Patients with reduced expression of MRP‐1/CD9 showed a significantly worse prognosis in overall survival (p = 0.005) and disease‐free survival (DFS; p < 0.0001) than those with stronger expression; and even among patients with stage‐I disease, similar results were obtained (overall survival, p = 0.038; DFS, p = 0.012). In a multivariate analysis, immunohistochemical MRP‐1/CD9‐expression level was an independent prognostic factor for DFS (p = 0.021), but not for overall survival (p = 0.572). Thus, immunohistochemical MRP‐1/CD9‐expression level solely in lung‐adenocarcinoma cells within the tumor tissue appears to be a prognostic factor for DFS, and may be useful for detecting a high‐risk sub‐group of recurrence during the post‐operative clinical course of the disease. Int. J. Cancer 74:205‐211, 1997.

Examination of in vitro chemosensitivity test using collagen gel droplet culture method with colorimetric endpoint quantification.

To develop a simpler method of performing the collagen gel droplet‐embedded culture drug sensitivity test (CD‐DST), we examined the introduction of colorimetric quantitative determination of images for evaluation of anticancer effect against cancer cells alone in the presence of fibroblasts, based on differences in proliferative morphology and stainability with neutral red of cells within collagen gel drops determined using a video‐microscope and NIH Image software. In examinations using a human cancer cell line and a fibroblast cell line, a high degree of linearity between number of cancer cells and image‐optical density was found within the range of 102–106 cells/droplet (r2=0.933). Using NIH Image, fibroblast cells could be eliminated at a cut‐off value of 128, and an immunocytochemical method demonstrated that the cells eliminated from the image were indeed fibroblasts, and those remaining were cancer cells. CD‐DST was carried out with mixtures of cancer cells with fibroblasts at various ratios, and the feasibility of evaluating anticancer activity in cancer cells alone with no effect of fibroblasts at any mixing ratio was confirmed. In addition, for CD‐DST of primary cell cultures of human lung cancers collected at the time of surgery, a high correlation between results obtained with the volume supplementation method, a current cell quantification method, and those with the imaging colorimetric quantification method was obtained (r=0.933). These results indicate that introduction of imaging colorimetric quantification utilizing NIH Image makes CD‐DST a quick and simple method that should be highly useful for clinical chemosensitivity testing using primary cell cultures of human cancers.

Surgery for pulmonary metastases from colorectal cancer: the importance of prethoracotomy serum carcinoembryonic antigen as an indicator of prognosis.

OBJECTIVE Several investigators have analyzed prognostic factors of surgical treatment for pulmonary metastases from colorectal cancer, but the results remain inconclusive. This study was performed to determine the prognostic implications of the prethoracotomy serum level of carcinoembryonic antigen (CEA) in relation to the postthoracotomy recurrent pattern among patients with this disease. METHODS A retrospective analysis of prognostic factors was undertaken in 100 patients who had consecutively undergone initial surgical resection for pulmonary metastases of colorectal origin. RESULTS The overall 3- and 5-year survival rates were 62.2% and 49.4%, respectively. Univariate analysis revealed that the prethoracotomy serum CEA level and operative curability were strongly associated with prognosis, while in multivariate analysis, only the prethoracotomy serum CEA level was a significant prognostic indicator. Patients with a high level of prethoracotomy serum CEA more frequently exhibited recurrence in extrathoracic sites, especially in the brain. CONCLUSION Before thoracotomy for pulmonary metastases from colorectal cancer, the serum CEA level was the most useful prognostic factor. Patients with elevated serum CEA level should undergo a careful prethoracotomy systemic survey and postthoracotomy follow-up for extrathoracic metastases, in particular brain metastases, and an appropriate combined therapeutic modality should be considered.

Pleural lavage cytology immediately after thoracotomy and before closure of the thoracic cavity for lung cancer without pleural effusion and dissemination: Clinicopathologic and prognostic analysis

AbstractBackground: The significance of intraoperative pleural lavage cytology (PLC) in lung cancer patients without malignant effusion remains undetermined in terms of staging, prognosis, and local management. Methods: PLC was performed both after thoracotomy and before closure of the thoracic cavity in 325 patients with lung cancer without malignant pleurisy. Results: According to the PLC results (positive [+] or negative [−] after thoracotomy/before closure), the patients were classified as follows: group A (−/−), 262 patients; group B (+/−), 19; group C (−/+), 22; and group D (+/+), 22. In comparison with group A, group C showed more advanced stage with aggressive nodal involvement, and group D showed more advanced lung cancer related to pleural and nodal involvement, whereas group B showed characteristics similar to those of group A. The rate of pleural recurrence in group D was the highest (26%). In particular, pleural recurrence was seen in the patients with a relatively large number of adenocarcinoma cells in PLC after thoracotomy. The patients in groups C and D, especially those with adenocarcinoma, showed poorer prognosis, but in a multivariate analysis, PLC status was not an independent prognostic factor. Conclusions: PLC status after thoracotomy provides useful information in the detection of high-risk subgroup for pleural recurrence. Although PLC status is closely associated with survival, its prognostic value is not independent.

bcl‐2 oncoprotein in surgically resected nonsmall cell lung cancer: Possibly favorable prognostic factor in association with low incidence of distant metastasis

The bcl‐2 oncoprotein serves a regulatory function in permitting several cell types to die in an apoptotic process. Its overexpression probably plays a role in tumorigenesis and tumor development. The aim of this study was to determine the clinicopathological and prognostic significance of the bcl‐2 oncoprotein in patients with nonsmall cell lung cancer (NSCLC).