Hepatocyte growth factor-induced calcium waves in hepatocytes as revealed with rapid scanning confocal microscopy.

Cytosolic Ca2+ transients induced by hepatocyte growth factor (HGF) were imaged in primary cultured rat hepatocytes using newly developed rapid scanning confocal microscopes and indo-1. HGF (40 ng/ml) increased cytosolic free Ca2+ concentration ([Ca2+]i) in about 60% of hepatocytes, in 45% of which the increases were oscillatory. In each of the oscillatory hepatocytes, the repetitive increases in [Ca2+]i originated from a specific same region adjacent to the cell membrane and propagated across the cell like waves. Phenylephrine (10 microM) also induced Ca2+ waves. The locus where HGF-induced Ca2+ waves and phenylephrine-induced Ca2+ waves were originated was the same, and there was a correlation in the peak height between HGF-induced Ca2+ waves and phenylephrine-induced Ca2+ waves in each cell, although the mechanisms of inositol 1,4,5-trisphosphate (ins(1,4,5)P3) formation induced by HGF should be different from those by phenylephrine. On the other hand, there was no correlation between sensitivity of each cell to HGF and that to phenylephrine which were measured as latent periods prior to Ca2+ rises after an addition of the agonists. These results suggested the following: the spatial patterns of Ca2+ waves were decided by a common mechanism, probably not the propagation of ins(1,4,5)P3 but the distribution of ins(1,4,5)P3-sensitive Ca2+ pools; sensitivities of each cell to the agonists did not mainly depend on the common mechanism.

Cancer cells isolated from malignant pleural and peritoneal effusions inhibit phospholipase A2 activity in human polymorphonuclear leukocytes.

We studied the influence of cancer cells on the LTB4 production by human polymorphonuclear leukocytes (PMN). The cancer cells were isolated from malignant pleural effusion specimens taken from two patients or from a peritoneal effusion specimen of one patient. While human PMN produced LTB4 following stimulation with A23187, the addition of cancer cells inhibited LTB4, 5-HETE and 12-HETE production by PMN in a cell number-dependent manner, while the cancer cell lines also showed a similar inhibition. The addition of lysate of the breast cancer cells also inhibited in a dose-dependent manner the production of LTB4 by PMN following stimulation with A23187. The addition of arachidonic acid completely reversed the inhibition of PMN-LTB4 production by the addition of the breast cancer cell lysates, thus suggesting inhibition at the phospholipase A2 level. The addition of this lysate to the partially purified human cytosolic PLA2 also inhibited the PLA2 activity. In contrast, the addition of lymphoma cells isolated from metastatic lymphnodes did not inhibit the LTB4 production from PMN. Since LTB4 is one of the important chemotactic factors for PMN and monocytes, these findings suggest that the inhibition of the PLA2 activity by the cancer cells thus results in a reduced production of LTB4 from PMN and contributes to a predisposition to develop severe infection in patients with advanced cancer.

Effect of tributyltin chloride on the release of calcium ion from intracellular calcium stores in rat hepatocytes.

The effects of tri-n-butyltin chloride (TBT), an environmental pollutant, on the release of Ca(2+) from intracellular stores were investigated in isolated rat hepatocytes. Isolated hepatocytes permeabilized with digitonin were suspended in solution, and the concentration of extracellular Ca(2+) was measured, using a fluorescent Ca(2+) dye, fura-2. In the solution containing permeabilized hepatocytes that had been preincubated with 4.0 microM TBT for 30 min, the extracellular Ca(2+) concentration was high, but the inositol 1,4,5-trisphosphate (InsP(3))-induced increase in Ca(2+) concentration was suppressed, suggesting that the extracellular release of Ca(2+) in response to TBT treatment was from intracellular stores. Images of the Ca(2+) concentration in the intracellular stores of primary cultured hepatocytes loaded with fura-2 were obtained after digitonin-permeabilization, using digitalized fluorescence microscopy. The permeabilized hepatocytes that had been preincubated with 4.0 microM TBT for 30 min had a very low fura-2 fluorescence ratio (340/380 nm), suggesting that stored Ca(2+) was released. When the hepatocytes were treated with 4.0 microM TBT after digitonin-permeabilization, the decrease in the fura-2 fluorescence ratio was very small. However, when the permeabilized hepatocytes were incubated with 4.0 microM TBT and 2.0 microM NADPH, the decrease was enhanced, raising the possibility that TBT might be metabolized to the active form(s), thus releasing Ca(2+) from intracellular stores. When the hepatocytes were preincubated with 0.1 microM TBT for 30 min and then were permeabilized, the fura-2 fluorescence ratio was almost the same as that in the control permeabilized hepatocytes. However, the InsP(3)-induced decrease in the fluorescence ratio was suppressed significantly in the permeabilized hepatocytes. These results suggest that TBT released Ca(2+) from the intracellular stores at high concentrations, and suppressed the InsP(3)-induced Ca(2+) release at non-toxic low concentrations. It is probable that the latter effect was responsible for the previously reported suppression of Ca(2+) response induced by hormonal stimulations (Kawanish et al., Toxicol Appl Pharmacol 1999;155:54-61).

Postrecurrent survival of patients with non-small-cell lung cancer undergoing a complete resection.

The postrecurrent survival of 215 patients who had undergone a complete resection of non-small-cell lung cancer was examined on the basis of various factors, which included gender (female, male), age (< 65, > or = 65), the pathologic stage of disease at the time of operation (I, II, III), histologic type (squamous cell, nonsquamous cell carcinoma), type of operation (pneumonectomy, other), the selection of adjuvant treatment before recurrence (no treatment, mild chemotherapy, intensive chemotherapy and/or radiotherapy), recurrent site (local, distant), and the disease-free interval (< or = 365, > or = 365 days). A univariate analysis of the postrecurrent survival showed that the significant factors influencing the survival consisted of gender, pathologic stage, recurrent site, selection of adjuvant treatment, and the disease-free interval. Namely, female patients or patients who had pathologic stage I disease, local recurrence, no adjuvant treatment, or a disease-free interval of more than 365 days would be expected to have a prolonged survival after recurrence. Of the five significant factors, only two factors (gender and the selection of the adjuvant treatment) were found to be predominant postrecurrent prognostic factors by multivariate analysis. These observations suggest that the biologic behavior of a recurrent tumor may therefore be influenced by gender and adjuvant treatment before recurrence.

Is T factor of the TNM staging system a predominant prognostic factor in pathologic stage I non-small-cell lung cancer ? A multivariate prognostic factor analysis of 151 patients.

We attempted to clarify whether the T factor of the TNM staging system should be viewed as a predominant prognostic factor in patients with pathologic stage I non-small-cell lung cancer when analyzed together with various histopathologic factors and deoxyribonucleic acid ploidy pattern of tumors. We studied 151 patients who were in this stage. Histopathologic factors used in the analysis were as follows: histologic cell type (squamous or nonsquamous cell carcinoma), grade of differentiation, and tumor invasion of visceral pleura and vessels. Deoxyribonucleic acid ploidy pattern of tumors was analyzed by flow cytometry, and the tumors were classified as diploid or aneuploid tumors. Significant prognostic factors (p < 0.05) that were demonstrated by univariate analysis of survival curves were as follows: (1) T1 versus T2; (2) well versus moderately or poorly differentiated tumor; (3) the absence versus presence of tumor exposed on pleura, (4) artery invasion, (5) lymphatic vessel invasion; and (6) diploid versus aneuploid tumor. Multivariate prognostic factor analysis showed the grade of differentiation and deoxyribonucleic acid ploidy pattern to be predominant prognostic factors. The T2 tumor group had significantly more cases with tumor invasion of lymphatic vessels that did the T1 tumor group and included 18 cases with tumor exposed on pleura. When these two factors were excluded from multivariate analysis, the T factor was marginally significant (p = 0.08). These observations suggest that the T factor is not necessarily a predominant prognostic factor in pathologic stage I non-small-cell lung cancer.

Hypotonic cisplatin treatment for carcinomatous pleuritis found at thoracotomy in patients with lung cancer. In vitro experiments and preliminary clinical results.

We have developed an intraoperative intrapleural treatment with the use of distilled water combined with cisplatin for carcinomatous pleuritis found at thoracotomy in patients with non-small-cell lung cancer. In the in vitro experiment, three different cell lines were used as a model of malignant pleural effusion. Cell growth was examined after a 3-day culture, which was preceded by exposure of the cells to cisplatin in either phosphate-buffered saline solution or distilled water for 1/2 to 5 minutes. The growth inhibition of tumor cells after hypotonic cisplatin treatment was significantly greater than after treatment with saline solution and cisplatin. Tumor that was obtained by resection of non-small-cell lung cancer was used as a model to demonstrate decreased viability of the tumor after exposure to hypotonic cisplatin. The viability of the tumor in a 6-day culture, preceded by exposure to hypotonic cisplatin (50 micrograms/ml) for 10 minutes, was markedly decreased. Intraoperative intrapleural hypotonic cisplatin was instilled in seven patients with pleural carcinomatosis without side effects and with control of pleural dissemination and pleural effusion for 6 to 29 months.

Prognostic factors obtained by a pathologic examination in completely resected non-small-cell lung cancer. An analysis in each pathologic stage.

We attempted to clarify what factors predominantly influence the survival of patients with non-small-cell lung cancer in each pathologic stage on the basis of information generally obtained by a pathologic examination of completely resected non-small-cell lung cancer. The subjects included 243 patients with stage I, 63 with stage II, and 108 with stage IIIA disease. Pathologic features used in the analysis were as follows: the greatest tumor size (< or = 3.0 cm versus > 3.0 cm), the histologic cell type (squamous versus nonsquamous cell carcinoma), the grade of differentiation, and tumor invasion of pleura and vessels. In stage IIIA, the extent of the metastasis to the lymph nodes was also included in the analysis. The significant prognostic factors (p < 0.05) in stage I demonstrated by a univariate analysis of the survival curves included the tumor size, the grade of differentiation (well differentiated versus moderately and poorly differentiated tumor), pleural involvement, and invasion of the artery and vein. In addition, the histologic cell type and the pleural involvement in stage II and invasion of the vein and the extent of metastasis to the lymph nodes (N0 and N1 versus N2) in stage IIIA were also found to be significant prognostic factors. A multivariate prognostic factor analysis showed that the grade of differentiation, pleural involvement, and venous invasion in stage I; the histologic cell type and pleural involvement in stage II; and venous invasion and mediastinal lymph node metastasis in stage IIIA were all predominant prognostic factors. These observations therefore suggest that a pathologic examination can identify the patients with a poor prognosis, which is different among the stages.

The first site of recurrence after complete resection in non-small-cell carcinoma of the lung. Comparison between pN0 disease and pN2 disease.

In the present study, we assessed whether the pattern of postoperative recurrence of non-small-cell lung cancer differed between patients with pathologic N0 disease and those with pathologic N2 disease. We reviewed 231 patients with pathologic N0 disease and 63 with pathologic N2 disease, who had undergone a complete resection from 1980 to 1990, and investigated the first recurrence sites. Seventy-two patients with pathologic N0 disease and 52 with pathologic N2 disease were found to have had postoperative recurrence. Both pathologic N0 disease and pathologic N2 disease recur frequently in distant organs, and the ratio of distant metastasis to local recurrence did not differ between the two diseases. The brain, lung, and bone were the common initial metastatic sites in both pathologic N0 disease and pathologic N2 disease. The brain was the most frequent site of distant metastasis in patients with pathologic N0 disease, whereas, on the other hand, pulmonary metastasis was observed more frequently than brain metastasis in those with pathologic N2 disease. Despite histologic types, the presence of different patterns of initial metastatic sites between pathologic N0 and pathologic N2 diseases was observed. Our results suggest that the sites of metastasis after resection depend largely on such anatomic factors as drainage routes. Namely, in contrast to pathologic N0 disease, pathologic N2 disease has an additional drainage route, which is from the N2 nodes to the superior vena cava (pulmonary circulation). Therefore, the frequency of pulmonary metastasis may increase in patients with pathologic N2 disease.

The correlation between tumor size and lymphatic vessel invasion in resected peripheral stage I non-small-cell lung cancer. A potential risk of limited resection.

We attempted to clarify whether a correlation exists between tumor size and the incidence of lymphatic vessel invasion in peripheral non-small-cell lung cancer without regional lymph node metastasis. The study included 212 resected non-small-cell lung cancers classified as pathologic stage I disease and located on the periphery of the lung. The incidence of lymphatic vessel invasion was relatively correlated with the maximum diameter of the tumor as follows: 25% (1/4) for tumor size 1.0 cm or less, 40% (19/48) for size 1.1 to 2.0 cm, 49% (28/58) for size 2.1 to 3.0 cm, and 57% (58/102) for tumor size 3.1 cm or more. The incidence of lymphatic vessel invasion of tumors measuring 3 cm or less in greatest dimension was 44% (48/110). The degree of lymphatic vessel invasion of 20 resected tumor samples measuring 3 cm or less in greatest diameter with hilar lymph node metastasis was also examined for comparison. This figure was as high as 85%. These observations suggest that even small peripheral tumors without any regional lymph node metastasis have a relatively high rate of lymphatic vessel invasion and thus pose a potential risk of local recurrence after a limited resection, especially in a wedge resection of the tumor.

Surgical results and prognostic factors of pathologic N1 disease in non-small-cell carcinoma of the lung. Significance of N1 level: lobar or hilar nodes.

The surgical outcome of pathologic N1 disease is controversial. To clarify whether pathologic N1 disease is a uniformly intermediate group or a mixed group of potentially early stage disease and advanced stage disease, we reviewed our previous cases with pathologic N1 disease. We retrospectively investigated 78 patients with pathologic N1 disease who had undergone a complete resection with mediastinal lymph node dissection during the period from April 1972 to December 1990. The cumulative postoperative survival at 5 years was 49.2%. No significant difference in the survival was found according to the following variables: sex, primary site, pathologic T factor, histologic type, type of resection, performance of adjuvant therapy. The lobar lymph nodes (Nos. 12 and 13) were only involved in 30 patients (38.5%), whereas the hilar nodes (Nos. 10 and 11) were involved in 48 patients (61.5%). The survival associated with lobar N1 disease was significantly better than that of hilar N1 disease (64.5% versus 39.7% at 5 years; p = 0.014). In lobar N1 disease, the brain was the most frequent site of distant metastasis, whereas the lungs were the most frequent site in hilar N1 disease. It was suggested that pathologic N1 disease is a mixed group of potentially early stage disease and advanced stage disease with regard to the postoperative prognosis.

Local recurrence after complete resection for non-small-cell carcinoma of the lung. Significance of local control by radiation treatment.

Of 471 patients undergoing a complete resection for non-small-cell carcinoma of the lung between 1972 and 1989, 40 patients (8.5%) had local recurrences without extrathoracic distant metastasis. Excluding 8 patients who had malignant pleural effusion, we selected 32 patients (24 with hilar-mediastinal lymph node, 6 with bronchial stump, and 2 with chest wall recurrence) from the 40 patients and assessed the significance of local control by radiotherapy. The median length of survival after disease recurrence for these 32 patients was 19 months. Of 29 patients given radiation treatment, 16 who responded to the treatment survived significantly longer than nonresponders (median survival time 27 months versus 6 months, p < 0.01). Univariate analyses of survival after recurrences in relation to various factors revealed that sex and disease-free intervals were significant prognostic factors (p < 0.05) other than the effect of radiotherapy. A multivariate analysis showed that the effect of radiotherapy was the predominant prognostic factor. From these results, we conclude that local control with radiation is beneficial in patients with solely locally recurrent tumors in terms of improved survival.

The diagnostic accuracy of a solitary pulmonary nodule, using thin-section high resolution CT: a solitary pulmonary nodule by HRCT.

A solitary pulmonary nodule (SPN) less than 2 cm in diameter of 60 patients was evaluated with thin-section, high-resolution computed tomography (HRCT). The presence of an irregular margin, speculation, convergence of the surrounding structure, an air bronchogram and the involvement of more than 3 vessels was observed more frequently in malignant nodules than in benign nodules. When one point was given for each finding, the mean total scores of each histologic type were as follows; adenocarcinoma; 2.7, squamous cell carcinoma; 2.5, benign tumor; 0.3, tuberculosis; 1.3, pneumonia; 2.0. When SPNs were classified by the total scores, the SPNs with higher scores (> or = 3) included 18 of 33 (56%) malignant lesions and only 2 of 28 (7%) benign lesions. This means that sensitivity and specificity in the diagnosis of malignancy in the SPNs with high scores were 56% and 93%, respectively. These observations suggest that SPNs with a score higher than 3 points would be highly suspicious for malignancy but the number of such SPNs is rather limited. Therefore, more sophisticated methods may be necessary to better differentiate between malignant and benign SPNs.

The clinical significance of serum soluble interleukin-2 receptors in lung cancer.

It has been recently reported that the soluble interleukin-2 receptor (IL-2R) levels in the sera of cancer patients were higher than those of normal controls. The present study was conducted in order to clarify the clinical significance of serum soluble IL-2R in patients with lung cancer. Using commercially available EIA kits, we measured the serum levels of soluble IL-2R in 102 lung cancer patients and 18 normal controls. The serum level of IL-2R was higher than 100 pM (mean +3 S.D. in the normal controls) in 14 of 58 patients with adenocarcinoma and in 13 of 32 patients with squamous cell carcinoma. In both adenocarcinoma and squamous cell carcinoma, the mean level of soluble IL-2R was higher in advanced stages (Stages IIIA, IIIB and IV) than in early stages (Stages I and II). In contrast, no patients with small cell carcinoma exhibited a serum level of soluble IL-2R higher than 100 pM, whereas almost all of those patients were in advanced-stage diseases. These results first demonstrated that the serum level of soluble IL-2R increased in association with both the disease stage and the histological type in lung cancer.

HLA class I and class II expression of pulmonary adenocarcinoma cells and the influence of interferon gamma.

BACKGROUND: The clinico-biological significance of HLA (both class I antigen and class II one) expressed on tumor cells still remains controversial. METHODS: Tumor cells were freshly separated from 33 surgical specimens of pulmonary adenocarcinoma. The tumor cells were incubated for 24 h in the presence or absence of IFN-gamma (130 International Units/ml). After incubation, the cells were cytocentrifuged onto glass slides and immunostained with either an anti-HLA class I (A, B, C) monoclonal antibody or anti-HLA class II (DR) one. RESULTS: In 22 of 33 cases (66.7%), the HLA class I were individually expressed by more than 60% of tumor cells while so were the HLA class II in 15 (45.4%). No significant correlation was observed between the HLA class I expression and the HLA class II one. The proportion of HLA class I-positive tumor cells correlated with neither the grade of histological differentiation nor the stage of disease. In contrast, the proportion of HLA class II-positive tumor cells correlated with both the grade of histological differentiation and the stage. In most cases, IFN-gamma was found to increase the proportion of class II-positive tumor cells as well as that of class I-positive cells. CONCLUSIONS: The above findings thus suggested that the HLA class II expression might therefore represent a manifestation of cellular differentiation and that IFN-gamma may, as a result, have the potential to differentiate cancer cells.

Interleukin-2 receptors in pulmonary adenocarcinoma tissue.

We previously reported that the serum soluble interleukin-2 receptor (sIL-2R) level increased with the advance of disease stage in non-small cell lung cancer. The present study was thus conducted to investigate the origin of serum sIL-2R in patients with pulmonary adenocarcinoma. Fresh tumor cell suspensions were prepared from surgically resected specimens of pulmonary adenocarcinoma. They were adjusted to a cell density of 5 x 10(5)/ml and then cultured for 24 h at 37 degrees C. The culture supernatants were collected and assayed to determine the sIL-2R levels using an enzyme immunoassay. The resultant cells were thereafter cytocentrifuged onto glass slides and immunochemically stained with anti-human IL-2R alpha (CD25) monoclonal antibody. In three of six cases examined, a substantial level of sIL-2R was identified in the culture supernatants. In four cases, including those three cases with the presence of sIL-2R in the culture supernatants, various proportions of tumor cells were positively stained with the anti-IL-2R alpha antibody. Further examinations revealed that tumor cells expressed IL-2R alpha (CD25) in seven of 16 cases with pulmonary adenocarcinoma. These results thus suggested that the tumor cells did express IL-2R alpha and release sIL-2R in some cases with pulmonary adenocarcinoma.

DNA ploidy patterns of tumors diagnosed as metachronous or recurrent lung cancers.

The relationship between the first tumor and the second tumor resected in 8 patients with non-small cell lung cancer was analyzed using deoxyribonucleic acid (DNA) flow cytometry. Of the 8 patients, 6 were clinically diagnosed as having metachronous lung cancers and 2, local recurrent tumors. The mean interval between operations in patients with metachronous lung cancers was 62 months (range, 15 to 128 months). Both tumors showed the same histology in 4 patients and a different histology in 2. In the 2 patients with local recurrent tumors, the interval between operations was 9 months and 39 months. In the analysis of DNA flow cytometry of the first and second tumors in the same patient, the tumors were defined as independent of each other when one tumor showed diploidy and the other, aneuploidy, or when each DNA index of abnormal clones between two aneuploid tumors was different. When both tumors showed diploidy or when at least one DNA index of abnormal clones between two aneuploid tumors was identical, the tumors were defined to be related to each other. According to these criteria, in 5 (83%) of the 6 patients clinically diagnosed as having metachronous lung cancers, the second tumor was classified as independent of the first tumor. On the other hand, in the 2 patients clinically diagnosed as having recurrent tumors, the second tumor was judged to be related to the first tumor. These data suggest that DNA flow cytometric analysis of tumors may be of value in the diagnosis of metachronous lung cancers.

Skip metastasis to the mediastinal lymph nodes in non-small cell lung cancer.

BACKGROUND: Whether any difference exists in clinical characteristics between resected non-small cell lung cancer with either skip or ordinary mediastinal lymph node metastases (N2 disease) needs to be clarified. METHODS: There were 110 patients with stage IIIA N2 disease. Thirty-three patients demonstrating no metastasis at the hilar nodes [skip (+) group] were compared with the other 77 patients [skip (-) group]. To investigate the extent of nodal involvement, we classified the mediastinal lymph nodes into three regions (superior, inferior, or aortic). RESULTS: There were no significant differences regarding histologic type, T status, or the site of the primary tumors between the skip (+) and the skip (-) N2 groups. In the skip (+) group, mediastinal node metastasis was found in only one region (level 1) in 30 patients (90.9%) and in two regions (level 2) in 3 (9.1%), whereas 28 patients (36.4%) from the skip (-) group revealed mediastinal metastasis at two or three regions (level 2 or 3). The overall survival rate at 5 years after operation was 35% in the skip (+) group and 12.7% in the skip (-) group (p = 0.054). This favorable clinical outcome in the skip (+) group could be explained partially by the higher proportion of patients with level 1 metastases. Furthermore, regarding patients with level 1 disease, the skip (+) group tended to have a better prognosis than the skip (-) group (p = 0.096). CONCLUSIONS: These results suggest that patients with skip mediastinal lymph node metastases represent a unique subgroup of N2 disease.

Diagnosis of visceral pleural invasion in resected lung cancer using a jet stream of saline solution.

BACKGROUND: Visceral pleural invasion by the tumor is an important prognostic factor in patients undergoing resection for lung cancer. We developed a method to detect more accurately the presence of visceral pleural invasion in resected lung cancer. METHODS: The surface of the visceral pleura over 90 resected peripheral tumors was irrigated twice with a jet stream of saline solution using a 20-mL syringe with a 21-gauge needle, and then the fluid, which contained desquamated cells, was collected for cytologic analysis. When cancer cells were found in the collected fluid, the tumor was judged to have invaded the visceral pleura. RESULTS: Thirty-eight (42%) resected tumors were identified as having visceral pleural invasion either by our new method or by pathologic examination. Twenty-four cases were detected by the jet stream of saline method alone, 5 by pathologic examination alone, and 9 by both techniques. The sensitivity and accuracy of the two approaches in the diagnosis of visceral pleural invasion were 87% and 94%, respectively, for our new method, and 37% and 73%, respectively, for pathologic examination (p < 0.0001). Furthermore, among 38 patients who had a tumor demonstrating visceral pleural invasion, 5 (13%) and 9 (24%) patients, respectively, had cancer cells in the pleural effusion and intrapleural lavage fluid. CONCLUSIONS: Our findings suggest that our method is useful in detecting cancer invasion of the visceral pleura, which is considered one of the causes of malignant effusion.

Results of a limited resection for compromised or poor-risk patients with clinical stage I non-small cell carcinoma of the lung.

BACKGROUND: Patients with stage I non-small cell carcinoma of the lung may be unable to undergo a standard curative resection, such as lobectomy, due to various medical reasons. Whether or not a limited resection is superior to radiotherapy in these patients, both in terms of long-term prognosis and treatment morbidity, is unknown. STUDY DESIGN: We retrospectively reviewed our results in treating compromised or poor-risk patients with clinical stage I non-small cell carcinoma of the lung who had received either a limited resection or radiotherapy. Seventeen patients underwent a limited resection (nine wedge resections and eight segmentectomies), while 18 patients received radiation therapy. RESULTS: The five-year survival rates for patients in the limited resection group and the radiation treatment group were 55.0 and 14.4 percent, respectively. A log-rank analysis showed a significant difference between the two groups (p = 0.004). Furthermore, the survival rate of the patients having a limited operation was significantly better than that of patients achieving either complete response or partial response from radiotherapy (18.8 percent at five years, p = 0.008). Recurrence at the surgical margin occurred in four patients in whom the tumor was greater than 2 cm in longest diameter. The incidence of severe treatment-related complications was not different between the limited operation group and the radiotherapy group (11.8 compared to 11.1 percent). CONCLUSIONS: The results indicate that a limited resection for patients with poor-risk clinical stage I carcinoma of the lung has an advantage over radiotherapy, especially for tumors measuring less than 2 cm in longest diameter.

Failure in resection of multiple pulmonary metastases from colorectal cancer.

BACKGROUND: To clarify whether or not multiple pulmonary metastases from colorectal cancer are contraindicated for a surgical resection, we retrospectively evaluated the influence of the number of pulmonary metastases on both the postthoracotomy survival and the pattern of the first failure. METHODS: From 1981 to 1993, 36 patients underwent a complete resection for pulmonary metastases from colorectal cancer. RESULTS: Of the various factors investigated including gender, primary site, disease-free interval, tumor size, the number of metastases, type of resection, and the history of hepatic metastases, only the number of pulmonary metastases was found to be significantly related to postthoracotomy survival. The rate of disease-free survival at 5 years was 62% for solitary metastasis (n = 17), 35% for two metastases (n = 8), and 0% for four or more metastases (n = 11). The pattern of failure also differed according to the number of pulmonary metastases. In particular, the incidence of local recurrence at the primary site increased with the number of pulmonary metastases (ie, 1 of 17 patients with a solitary metastasis, 3 of 8 with two metastases, and 6 of 11 with four or more metastases). CONCLUSIONS: These results suggest that multiple metastases might indicate the presence of local recurrence at the primary site; therefore, in cases of multiple pulmonary metastases, the primary site should be thoroughly explored.