Resection of multifocal non-small cell lung cancer when the bronchioloalveolar subtype is involved

OBJECTIVE: Bronchioloalveolar lung cancer is commonly multifocal and can also present with other non-small cell types. The staging and treatment of multifocal non-small cell cancer are controversial. We evaluated the current staging of multifocal bronchioloalveolar carcinoma and the therapeutic effectiveness of resection when this tumor type is involved. METHODS: We reviewed our experience between 1992 and 2000 with complete pulmonary resections for bronchioloalveolar carcinoma. Kaplan-Meier survival curves were calculated from the dates of pulmonary resection. RESULTS: Among 73 patients with bronchioloalveolar carcinoma, 14 patients, 7 male and 7 female with a mean age of 65 years (51-87 years), had multifocal lesions without lymph node metastases. Follow-up was 100% for a median of 5 years (range 2.6-8.5 years). Tumor distribution was unilateral in 9 patients and bilateral in 5 patients. The multifocal nature of the disease was discovered intraoperatively in 4 patients. Nine patients had 2 lesions, 4 patients had 3 lesions, and 1 patient had innumerable discrete foci in a single lobe. Operative mortality was 0. Postoperatively, 10 patients were staged pIIIB or pIV on the basis of multiple foci of similar morphology; 4 patients had some differences in histology (implying multiple stage 1 primaries). The median survival time to death from cancer was 14 months (141 days-5.6 years). The overall 5-year survival after resection of multifocal bronchioloalveolar carcinoma was 64%. Unilateral or bilateral distribution had no impact on survival. CONCLUSIONS: The current staging system is not prognostic for multifocal bronchioloalveolar carcinoma without lymph node metastases. Complete resection of multifocal non-small cell lung cancer when bronchioloalveolar carcinoma is a component may achieve survivals similar to that of stage I and II unifocal non-small cell lung cancer. When bronchioloalveolar carcinoma is believed to be one of the cell types in multifocal disease without lymph node metastases, consideration should be given to surgical resection.     

A prospective study of adjuvant surgical resection after chemotherapy for limited small cell lung cancer. A University of Toronto Lung Oncology Group study

Seventy-two patients with limited small cell lung cancer were identified as candidates for adjuvant operation after chemotherapy. All patients received preoperative chemotherapy with cyclophosphamide, doxorubicin HCl (Adriamycin), and vincristine, or the epipodophyllotoxin derivative VP-16 and cisplatin. The rate of response to chemotherapy was 80% (complete response 38% and partial response 42%). After chemotherapy, 57 patients (79.1%) were candidates for adjuvant surgical resection, but only 38 underwent thoracotomy. Eight required a pneumonectomy, 25 a lobectomy, and five patients had no resection. Postoperative pathologic study revealed only small cell lung cancer for 29 patients, mixed and non-small cell lung cancer for two, non-small cell lung cancer for four, and no residual tumor in three patients. Pathologic staging revealed seven patients in stage I (N0), nine in stage II (N1), and 22 in stage III. The median survival time for the 38 surgical patients was 91 weeks and projected 5-year survival rate 36%. Patients with pathologic stage I disease had significantly longer survival times (median not reached) than did patients in stage II or stage III (median survival 69 and 52 weeks, respectively). Within the group not undergoing operation, 19 patients responded to therapy and were eligible for adjuvant surgical resection, but did not undergo thoracotomy (10 patients were randomized to radiation only, and nine patients refused operation). Their median survival of 51 weeks was inferior to that of the 38 surgical patients (p = 0.049). Adjuvant surgical resection after chemotherapy resulted in long-term survival and cure for a significant proportion of patients with pathologic stage I disease. A significant improvement in survival could not be documented for patients in stages II and III. Intensive pretreatment investigation including mediastinoscopy is essential to exclude patients who will not benefit from adjuvant surgical resection.     

Large cell neuroendocrine carcinoma of the lung: a clinicopathologic study of eighty-seven cases

OBJECTIVE: Large cell neuroendocrine carcinoma of the lung is a newly recognized clinicopathologic entity. The clinical characteristics and optimal treatment of patients with large cell carcinomas are not yet established. The aim of this study was to define the clinicopathologic characteristics of large cell neuroendocrine carcinoma. METHODS: The histologic characteristics of the patients receiving an initial diagnosis of poorly differentiated non-small cell lung carcinoma (n = 484), small cell carcinoma (n = 55), carcinoid (n = 31), and large cell neuroendocrine carcinoma (n = 12) were retrospectively reviewed according to World Health Organization criteria. Immunohistochemistry was performed to confirm the neuroendocrine phenotype. The outcomes and other clinical characteristics of those patients with large cell neuroendocrine carcinoma were retrospectively analyzed and compared with those of patients with poorly differentiated carcinoma of other histologic types. RESULTS: A total of 87 patients were given a diagnosis of large cell neuroendocrine carcinoma after the histologic review. These patients comprised 3.1% of all patients undergoing resection for primary lung cancer during the same period. The overall 5-year survival was 57%. The 5-year survivals of patients with stage I, II, III, and IV disease were 67%, 75%, 45%, and 0%, respectively. There was no statistically significant difference between the overall survival of patients with large cell neuroendocrine carcinoma and those with other non-small cell lung cancers. There was a significant difference between the survival of patients with stage I large cell neuroendocrine carcinoma and that of patients with the same stage of other non-small cell lung carcinomas. The site of the first documented recurrence was locoregional in 12 patients (34%), distant metastases in 20 patients (57%), and both simultaneously in 3 patients. Locoregional lymph node recurrences were observed frequently. More than 80% of recurrences were found within 1 year after the operation. CONCLUSION: In terms of prognosis, large cell neuroendocrine carcinoma is distinctly different from other non-small cell lung cancers. The prognosis of large cell neuroendocrine carcinoma was poor, even for early stage disease; the prognosis of the stage I disease of large cell neuroendocrine carcinoma was poorer than that of the same stage of other non-small cell lung cancers. Because of its aggressive clinical behavior and poor prognosis, large cell neuroendocrine carcinoma should be recognized as one of the poorest prognostic subgroups among primary lung cancers, and therefore novel therapeutic approaches should be established.     

Prognostic significance of E-cadherin and beta-catenin in resected stage I non-small cell lung cancer.

OBJECTIVES: E-cadherin and its associated intracellular molecules, catenins, are important for cell-cell adhesion. Impaired expression of these molecules are frequently observed in several cancers. E-cadherin and beta-catenin are often expressed in non-small cell lung cancers. The aim of this study was to investigate the expressions of E-cadherin and beta-catenin and their significance as prognostic markers in pathological stage I non-small cell lung cancer. METHODS: Paraffin embedded tumor tissue blocks were obtained from 141 patients who underwent resection without preoperative radiotherapy or chemotherapy with pathological stage I non-small cell lung cancer. Tumor samples were prepared in tissue microarrays and they were stained by immunohistochemistry with antibodies against E-cadherin and beta-catenin. The expressions of E-cadherin and beta-catenin were analyzed with relation to the clinico-pathological data. The median follow-up period of the patients was 41 months (range, 2-88 months). RESULTS: Preserved expressions of E-cadherin and beta-catenin were observed in the membrane and the cytoplasm of normal epithelial cells and tumor cells. Absent or reduced expression for E-cadherin and beta-catenin were observed in 60% and 45% of all the patients, respectively. There was a significant positive correlation between E-cadherin and beta-catenin expression (P<0.01). Absent or reduced expression of E-cadherin was observed in 72.5%, 36.6%, and 60.0% of squamous cell carcinoma, adenocarcinoma, and bronchioloalveolar carcinoma, respectively. There was a significant decrease of E-cadherin expression in squamous cell carcinoma compared to adenocarcinoma (P<0.01). Patients with reduced expression of beta-catenin had poor recurrence free survival in adenocarcinoma, but not in squamous cell carcinoma. CONCLUSION: Decreased expressions of E-cadherin and beta-catenin were closely correlated in resected stage I non-small cell lung cancer. Reduced expression of E-cadherin and beta-catenin indicates tumor cell dedifferentiation and reduced expression of beta-catenin had poor recurrence free survival in adenocarcinoma of the resected stage I non-small cell lung cancer.     

Surgical treatment of solitary adrenal metastasis from non-small cell lung cancer

BACKGROUND: Management of solitary adrenal metastasis from non-small cell lung cancer is still debated. Although classically considered incurable, various reports with small numbers of patients have shown that surgical treatment might improve long-term survival. The aim of this study was to review our experience and to identify factors that could affect survival. METHODS: From January 1989 through April 2003, 23 patients underwent complete resection of an isolated adrenal metastasis after surgical treatment of non-small cell lung cancer. There were 19 men and 4 women, with a mean age of 54 +/- 10 years. The diagnosis of adrenal metastasis was synchronous with the diagnosis of non-small cell lung cancer in 6 patients and metachronous in 17 patients. The median disease-free interval for patients with metachronous metastasis was 12.5 months (range, 4.5-60.1 months). RESULTS: The overall 5-year survival was 23.3%. Univariate and multivariate analysis demonstrated that a disease-free interval of greater than 6 months was an independent and significant predictor of increased survival in patients after adrenalectomy. All patients with a disease-free interval of less than 6 months died within 2 years of the operation. The 5-year survival was 38% after resection of an isolated adrenal metastasis that occurred more than 6 months after lung resection. Adjuvant therapy and pathologic staging of non-small cell lung cancer did not affect survival. CONCLUSIONS: Surgical resection of metachronous isolated adrenal metastasis with a disease-free interval of greater than 6 months can provide long-term survival in patients previously undergoing complete resection of the primary non-small cell lung cancer.     

Is lung cancer surgery justified in patients with direct mediastinal invasion?

OBJECTIVE: To assess the results of the surgical treatment of patients with stage IIIB non-small cell lung carcinoma (NSCLC) invading the mediastinum (T4). METHODS: Twenty-nine patients were operated on from 1986 to 1999. Histology was squamous cell carcinoma in 17 patients, adenocarcinoma in eight, large cell carcinoma in two and neuroendocrinal carcinoma in two. Three patients received a preoperative chemotherapy (n = 2) or radiochemotherapy (n = 1). The lung resection consisted of a pneumonectomy in 25 patients and a lobectomy in four. The procedure was extended to one of the following structures: superior vena cava (SVC) (n = 17), aorta (n = 1), left atrium (n = 5) and carina (n = 6). Seventeen patients had a postoperative regimen including radiochemotherapy (n = 12), radiotherapy (n = 4), or chemotherapy (n = 1). RESULTS: Complete R0 resection was achieved in 25 patients, whereas four patients had a microscopically (n = 1) or macroscopically (n = 3) residual disease. The operative mortality rate was 7% (n = 2). Non-fatal major complications occurred in eight patients (28%). Overall 5-year survival rate was 28% (median 11 months), including the operative mortality. The median survival of the 18 patients with an N0 or N1 disease was 16 months whereas the median survival of the 11 patients with an N2 disease was 9 months. At completion of the study, 22 patients have died, two postoperatively and 10 from pulmonary causes without evidence of cancer. CONCLUSIONS: Surgical management of T4 NSC lung cancer invading the mediastinum should be considered, in the absence of N2 disease, when a complete resection is achievable.     

非小细胞肺癌术后支气管切缘癌与预后

为探讨肺癌术后支气管切缘癌的发生率及预后特点，提高肺癌５年生存率，回顾总结１９８１～１９９０年经手术治疗１０２４例非小细胞肺癌，显微镜下发现支气管残端癌阳性者８９例占８．７％。此８９例病人平均５年生存率２３．７％。中位数生存期２７．６个月。其中ＰＴＮＭＩ、ＩＩ、ＩＩａ和ＩＩｂ期病人平均生存期分别为４４．３、２７．１、１２．４和１２．６个月，鳞癌、腺癌、大细胞癌及鳞腺混合癌病人的平均生存期分别为３１．０、１９．３、１４．８和２８．３个月。结论：影响病人预后的因素主要是病变的ＴＮＭ分期及细胞类型，对有残端癌的病人应强调术后综合治疗     

Surgical treatment of primary lung cancer with synchronous brain metastases

OBJECTIVES: The role of surgical resection for brain metastases from non-small cell lung cancer is evolving. Although resection of primary lung cancer and metachronous brain metastases is superior to other treatment modalities in prolonging survival and disease-free interval, resection of the primary non-small cell lung cancer and synchronous brain metastases is controversial. METHODS: From January 1975 to December 1997, 220 patients underwent surgical treatment for brain metastases from non-small cell lung cancer at our institution. Twenty-eight (12.7%) of these patients underwent surgical resection of synchronous brain metastases and the primary non-small cell lung cancer. RESULTS: The group comprised 18 men and 10 women. Median age was 57 years (range 35-71 years). Twenty-two (78.6%) patients had neurologic symptoms. Craniotomy was performed first in all 28 patients. Median time between craniotomy and thoracotomy was 14 days (range 4-840 days). Pneumonectomy was performed in 4 patients, bilobectomy in 4, lobectomy in 18, and wedge excision in 2. Postoperative complications developed in 6 (21.4%) patients. Cell type was adenocarcinoma in 11 patients, squamous cell carcinoma in 9, and large cell carcinoma in 8. After pulmonary resection, 17 patients had no evidence of lymph node metastases (N0), 5 had hilar metastases (N1), and 6 had mediastinal metastases (N2). Twenty-four (85.7%) patients received postoperative adjuvant therapy. Follow-up was complete in all patients for a median of 24 months (range 2-104 months). Median survival was 24 months (range 2-104). Survival at 1, 2, and 5 years was 64.3%, 54.0%, and 21.4%, respectively. The presence of thoracic lymph node metastases (N1 or N2) significantly affected 5-year survival (P =.001). CONCLUSION: Although the overall survival for patients who have brain metastases from non-small cell lung cancer is poor, surgical resection may prove beneficial in a select group of patients with synchronous brain metastases and lung cancer without lymph node metastases.     

Large cell carcinoma of the lung: results of resection for a cure

OBJECTIVE: The effectiveness of surgical resection of large cell undifferentiated carcinoma of the lung remains poorly defined because of the histology's relatively low frequency, the tendency for presentation with high-stage disease, and the failure in most published series to separate large cell carcinomas from the other variants of non-small cell lung carcinoma. To define the effectiveness of surgical treatment of large cell carcinoma, we reviewed the Mayo Clinic experience over a 5-year period. METHODS: We have retrospectively reviewed the Mayo Clinic experience with 61 patients with large cell carcinoma and 17 patients with adenocarcinoma with focal mucin production who came to surgical resection during the 5-year period of January 1, 1982, through December 31, 1986. RESULTS: One-hundred percent 5-year follow-up was obtained. For the 61 patients with large cell carcinoma, the overall 5-year survival was 37%. Five-year survival for those with stage I tumors was 58% (n = 31), stage II 33% (n = 6), stage IIIA 15% (n = 20), stage IIIB 0% (n = 2), and stage IV 0% (n = 2). No significant differences in survival were detected between the 61 patients with large cell carcinoma and the 17 patients with solid adenocarcinoma with mucin production. CONCLUSIONS: Our results suggest that there is a subset of patients with large cell carcinoma of the lung who can undergo resection with a reasonable expectation of long-term survival and that this survival is, stage for stage, comparable to or only slightly less than that achieved with other non-small cell lung carcinomas.     

Flow cytometric analysis of cellular DNA content of lung cancer with reference to survival

The cellular DNA content of lung cancer were measured by flow cytometry on 223 paraffin-embedded specimens prepared from resected lung carcinomas. According to the histological type of lung cancer, the mean values for the DNA Index were 1.41 in adenocarcinoma, 1.39 in squamous cell carcinoma, 1.33 in large cell carcinoma and 1.84 in small cell carcinoma. The DNA Index of small cell carcinoma was thus slightly higher than that of the other histological types, without statistically significant difference. Of 223 lung carcinoma cases, 131 (59.1%) were DNA aneuploidy and 92 (40.9%) were DNA diploidy. DNA aneuploidy was found in 56.1% of adenocarcinomas, 59.5% of squamous cell carcinomas, 53.3% of large cell carcinomas and 100% of small cell carcinomas. According to the staging of the lung cancer, the mean values of the DNA Index were 1.40 in stage I, 1.46 in stage II, 1.36 in stage IIIA, 1.48 in stage IIIB and 1.48 in stage IV. No statistically significant differences were found among these stages. DNA aneuploidy was found in 57.1% of stage I, 57.9% of stage II, 54.7% of stage IIIA, 60.0% of stage IIIB and 75.0% of stage IV. The correlation of DNA content with survival were investigated in 94 cases with stage I non-small cell carcinoma which underwent absolute curative resection. Of 94 cases, the 5-year survival rate of 40 cases with DNA diploidy was 81.1% and a mean survival time 111 months, while this one of the remaining 54 with DNA aneuploidy was 58.4% and a mean survival time 80 months.(ABSTRACT TRUNCATED AT 250 WORDS)     

Prognosis and survival of pT1N2 lung carcinoma undergoing pulmonary resection and mediastinal lymph node dissection

In the past 15 years, mediastinal lymph node dissection in conjunction with pulmonary resection was performed on 39 pT1N2 patients at Tokyo Metropolitan Komagome Hospital. The patients consisted of 4 histological cell types: 26 adenocarcinomas, 5 epidermoid carcinomas, 4 large cell carcinomas and 4 small cell carcinomas. The absolute five-year survival rate for pT1 N2 patients undergoing curative resection was 52.7% which was better than that of patients with stage II non-small cell carcinoma surgically resected during the same period. This finding suggests that pT1N2 group is a special entity among pN2 lung carcinoma, that shows better survival rate than less advanced patients with respect to pathological stage (stage II).     

Visceral pleura invasion by non-small cell lung cancer: an underrated bad prognostic factor

BACKGROUND: Visceral pleura invasion (VPI) by non-small cell lung cancer is a factor of poor prognosis. A tumor of any size that invades the visceral pleura is classified as T2. Few studies have been conducted concerning the prognostic significance of VPI relative to other staging factors. METHODS: Between April 1984 and December 1996, 1,281 patients with T1 (n = 430) and T2 (n = 851) non-small cell lung cancer underwent curative surgical resection. Adjuvant radiation therapy was performed in 455 patients. There were 176 women and 1,105 men aged 30 to 86 years (mean, 60.9 years). Five hundred nineteen pneumonectomies, 742 lobectomies, and 20 segmentectomies were performed. In all patients, a complete mediastinal lymph node dissection was performed. International staging was stage IA and B (n = 697); stage II A and B (n = 247), and stage III A (n = 337). The patients were divided into two groups according to the existence of VPI (group I without, group II with). Both groups were compared with regard to the size of the tumors, histology, associated lymph node involvement, survival rates, and cause of death. Univariate and multivariate analyses were conducted. RESULTS: VPI (group II) was identified in 19.1% of the resected specimens: group I, n = 1036; group II, n = 245. The VPI was present in only 10% of non-small cell lung cancer 3 cm or less in size, reaching 33% of patients with non-small cell lung cancer larger than 5 cm (p = 0.0001). Squamous non-small cell lung cancer were significantly less accompanied by VPI (13.5%) than the other histologic categories. The VPI was associated with a higher frequency of N2 involvement (group I = 24.6%, group II = 33.4%, p = 0.01) and N2 involvement was more extensive (two or more N2 involved stations: group I = 8.2%, group II = 15.6%, p = 0.003). Actuarial survival rates were 51.8% at 5 years and 33.8% at 10 years in group I (median, 66 months), and 34.6% at 5 years and 27.9% at 10 years in group II (median, 30 months) (p = 0.000002). Long-term survival rates significantly decreased for larger tumors. Even in patients with N2 stage tumors, the difference of survival curves between the two groups was statistically significant. Cancer-related deaths were more frequent in group II and were mainly caused by distant metastases. By multivariate analysis, visceral pleura invasion proved to be a significant independent factor of poor prognosis. CONCLUSIONS: The VPI is a factor of poor prognosis. Its frequent association with extensive N2 involvement supports the hypothesis that exfoliated tumor cells are drained through the pleural lymphatics by the mediastinal lymphatic pathways and then into the bloodstream. The VPI is an important prognostic factor and, as such should stimulate more studies to better select the patients who could benefit from adjuvant therapy.     

Comparison of mutational changes in involved N1 lymph nodes with those in primary tumors in stage II non-small cell lung cancer: a pilot study

OBJECTIVES: Surgical resection is the standard treatment for stage II non-small cell lung cancer, but recurrence rates approach 60%. This study compared mutational changes in involved lymph nodes and primary tumors from patients with stage II non-small cell lung cancer to determine whether risk factors for recurrence could be identified. METHODS: Forty patients with resected stage II non-small cell lung cancer (excluding T3 N0 disease) were studied. Microdissection was performed on primary tumors and lymph nodes. Analysis was performed across 9 genomic loci by using polymerase chain reaction amplification. The ratio of fractional allelic loss between involved lymph nodes and primary tumors was used to stratify patients into high-risk (fractional allelic loss ratio of >or=1) and low-risk (fractional allelic loss ratio of <1) groups. RESULTS: The median age of the patients was 68 years (range, 42-85 years). Median follow-up was 30 months. Fractional allelic loss was greater in patients with squamous carcinomas compared with that in adenocarcinomas, but survival was similar (35 vs 39 months). The median survival was 35 months in high-risk patients and was not reached in low-risk patients (P =.3). Disease-free survival was 24 months in high-risk patients and was not reached in low-risk patients (P =.35). In the subset with adenocarcinoma (n = 18), median survival was 24 months in the high-risk group; no deaths occurred in low-risk patients (P =.01). Also, disease-free survival was 14 months in high-risk patients and was not reached in the low-risk patients (P =.05). CONCLUSIONS: Squamous cancers demonstrate greater mutational changes than adenocarcinomas; this does not affect outcome. The patients with low-risk adenocarcinomas demonstrated superior outcomes compared with those of other patients. These results should be confirmed in larger studies.     

Surgical treatment for limited small-cell lung cancer. The University of Toronto Lung Oncology Group experience.

Since 1977, 119 patients with limited small-cell lung cancer have undergone combined modality therapy including surgery at our institution. Seventy-nine patients (58 male, 21 female; median age 63 years) had surgery first, and 67 of these had adjuvant chemotherapy. Forty (27 male, 13 female; median age 59 years) had chemotherapy first, and 94% had a complete or partial response before the operation. Pretreatment staging revealed 69 stage I, 27 stage II, and 23 stage III tumors. Twenty-six patients required pneumonectomy, 88 lobectomy, and five had no resection. Four patients had gross and six had microscopic residual disease. Postoperative pathologic examination showed small-cell lung cancer only (n = 95), non-small-cell lung cancer (n = 3), mixed (n = 17), and no residual tumor (n = 4). Postoperative staging revealed 35 stage I, 36 stage II, and 48 stage IIIa tumors. The median survival of the entire group is 111 weeks and the projected 5-year survival rate is 39%. No survival difference was seen between patients treated with chemotherapy before the operation and those undergoing an initial operation followed by chemotherapy (p = 0.756). The median survival for patients with pathologic stage I disease has not been reached, and the projected 5-year survival rate is 51%. This is significantly better than for the patients with stage II (median 82 weeks, p = 0.001) or stage III (median 83 weeks, p = 0.001) disease, who have projected 5-year survival rates of 28% and 19%, respectively. Seven of the 12 patients who had no adjuvant chemotherapy remain alive at 6 to 48+ months. Sixty-seven patients have died (11 had no evidence of disease). Only 10 patients had a relapse in the primary site alone, seven at the primary and distant sites, and 39 only in distant sites. In summary, resection improves control at the primary site, and a significant proportion of patients with stage I (N0) disease achieve long-term survival and cure with combined modality therapy including surgery. Stage II and IIIa patients have survival predictions similar to stage IIIa non-small-cell lung carcinoma treated surgically.     

Surgical treatment of non-small cell lung cancer 1 cm or less in diameter

BACKGROUND: Routine lung cancer screening does not currently exist in the United States. Computed tomography can detect small cancers and may well be the screening choice in the future. Controversy exists, however, regarding the surgical management of these small lung cancers. METHODS: The records of all patients were reviewed who underwent resection of solitary non-small cell lung cancers 1 cm or less in diameter from 1980 through 1999. RESULTS: The study included 100 patients (56 men and 44 women) with a median age of 67 years (range 43 to 84 years). Lobectomy was performed in 71 patients, bilobectomy in 4, segmentectomy in 12, and wedge excision in 13. Ninety-four patients had complete mediastinal lymph node dissection. The cancer was an adenocarcinoma in 48 patients, squamous cell carcinoma in 26, bronchioloalveolar carcinoma in 19, large cell carcinoma in 4, adenosquamous cell carcinoma in 2, and undifferentiated in 1. Tumor diameter ranged from 3 to 10 mm. Seven patients had lymph node metastases (N1, 5 patients; N2, 2 patients). Postsurgical stage was IA in 92 patients, IB in 1, IIA in 5, and IIIA in 2. There were four operative deaths. Follow-up was complete in all patients and ranged from 4 to 214 months (median 43 months). Eighteen patients (18.0%) developed recurrent lung cancer. Overall and lung cancer-specific 5-year survivals were 64.1% and 85.4%, respectively. Patients who underwent lobectomy had significantly better survival and fewer recurrences than patients who had wedge excision or segmentectomy (p = 0.04). CONCLUSIONS: Because recurrent cancer and lymph node metastasis can occur in patients with non-small cell lung cancers 1 cm or less in size, lobectomy with lymph node dissection is warranted when medically possible.     

Diagnosis and treatment of lung cancer – Non-small cell lung cancer, small cell lung cancer and carcinoids

Summary BACKGROUND: The prognosis of lung tumors is determined by histology and staging (nodal status). The most common tumor is non-small cell lung carcinoma (NSCLC) with a 5-year survival rate of 67 % (stage IA) to <5 % (stage IV). METHODS: By reviewing the literature guidelines for diagnosis and treatment of non-small cell lung cancer and neurendocrine tumors are presented. RESULTS: Functional operability provided, (bi)lobectomy or pneumonectomy with mediastinal lymph node dissection are the standard procedures. In case of positive mediastinal lymph nodes (stage IIIA/IIIB) induction chemo(radio)therapy is indicated. Cervical mediastinoscopy is performed in patients with enlarged mediastinal nodes (CT >1 cm), especially in PET-positive cases. Adjuvant chemotherapy is used in clinical trials. Small-cell lung cancer (SCLC, neuroendocrine tumor grade III) has a poor prognosis, and is treated with chemotherapy; resection may be performed in early stages. Neuroendocrine tumors grade I (typical carcinoid) are resected by segmentectomy, lobectomy, or bronchoplastic resection. Neuroendocrine tumors grade II (atypical carcinoids) are treated like NSCLC. CONCLUSIONS: The incidence of lung cancer is decreased by tobacco control, and the chances of survival are improved by early detection and multimodality regimens.      

Bronchoplastic procedures in malignant and nonmalignant disease: multivariable analysis of 144 cases

OBJECTIVES: We sought to analyze the experience with bronchoplastic procedures over a 7-year period and to determine putative prognostic factors for survival. METHODS: From 1991 to 1997, 144 bronchoplastic procedures were performed for non-small cell lung cancer (n = 123), small cell lung cancer (n = 5), carcinoid tumor (n = 10), and metastases of extrathoracic malignant tumors (n = 6). There were 111 sleeve lobectomies, 17 bilobectomies, 4 lobectomies with carinal resection, 8 sleeve pneumonectomies, and 4 bronchotomies without parenchymal resection. Multivariable analysis included risk factors, such as age, sex, type of bronchoplastic procedure (bronchotomy, lobectomy, bilobectomy, or pneumonectomy), additional angioplasty, TNM staging, histology, radicality of resection, respiratory risk (forced expiratory volume in 1 second, percent predicted < 60), cardiovascular risk, and adjuvant therapy. RESULTS: Overall 1- and 3-year survival was 72% and 52%, respectively. The overall 30-day mortality was 8.3% (5.4% for single sleeve lobectomies). Multivariable analysis demonstrated 4 risk factors for survival. High tumor stage, type of bronchoplastic procedure, impaired lung function, and presence of cardiovascular risk were associated with a poor outcome. Univariate analysis showed reduced survival in patients with sleeve pneumonectomies (1-year survival, 25%). CONCLUSIONS: Bronchoplastic procedures for central tumors and sleeve pneumonectomies are associated with poor survival. Careful selection of these patients, as well as of patients with impaired lung function and cardiovascular risk factors, is mandatory.     

Nodal stage after induction therapy for stage IIIA lung cancer determines patient survival

Background. This study was undertaken to determine the predictive value of nodal status at resection in regards to long-term outcome of patients undergoing neo-adjuvant therapy and resection for stage IIIA N2-positive non-small cell lung cancer (NSCLC).

Methods. We reviewed the medical records of all patients found on surgical staging to have N2-positive NSCLC and who underwent induction therapy followed by resection between 1988 and 1996 at our hospital. Complete follow-up information was examined utilizing Kaplan-Meier survival analysis and Cox proportional hazards multivariate analysis.

Results. One hundred three patients (59 men) with stage IIIA N2-positive NSCLC received neoadjuvant therapy before surgical resection. Preoperative therapy consisted of platinum-based chemotherapy (76), radiotherapy (18), or chemoradiation (9). Operations included pneumonectomy (38), bilobectomy (6), and lobectomy (59). There were four deaths and seven major complications. Eighty-five patients were followed until death. Median survival among 18 living patients is 60.9 months (range 29 to 121 months). Twenty-nine patients were downstaged to N0 and had 5-year survival of 35.8% (median survival 21.3 months). Seventy-four patients with persistent tumor in their lymph nodes (25 N1 and 49 N2) had significantly worse, 9%, 5-year survival, p = 0.023 (median survival 15.9 months). Other negative prognostic factors were adenocarcinoma and pneumonectomy.

Conclusions. Patients with N2-positive NSCLC whose nodal disease is eradicated after neoadjuvant therapy and surgery enjoy significantly improved cancer-free survival. These data support surgical resection for patients downstaged by induction therapy; however, patients who are not downstaged do not benefit from surgical resection. Direct effort should be made to improve the accuracy of restaging before resection.     

Prognostic significance of preoperative serum carcinoembryonic antigen level in lung adenocarcinoma but not squamous cell carcinoma.

OBJECTIVES: Clinical significance of measurement of preoperative serum carcinoembryonic antigen (CEA) level in patients with non-small cell lung cancer was investigated. METHODS: Consecutive 271 adenocarcinoma and 112 squamous cell carcinoma patients of non-small cell lung cancer referred to our institute were included in this study. There were 214 men and 169 women, ages ranged from 19 to 90 years, with an average of 64.46 years. Curative resection was performed for 220 adenocarcinoma and 93 squamous cell carcinoma patients. Serum level of CEA was measured before staging or resection of cancer. RESULTS: There is a trend toward a correlation between serum CEA level and stage of the diseases, however, serum CEA level was not always related to tumor node metastasis (TNM) status. In patients with adenocarcinoma, survival rate of patients with an elevated serum CEA level was significantly lower than that with a normal serum CEA level. Multivariate analysis showed that prognostic significance of serum CEA level was TNM staging independent in patients with adenocarcinoma. On the other hand, serum CEA level was not related to patients' survival in patients with squamous cell carcinoma. CONCLUSIONS: Elevated preoperative serum CEA level is a TNM staging independent prognostic factor for patients with adenocarcinoma but not for those with squamous cell carcinoma.     

The role of adjuvant therapy after resection of T1 N1 M0 and T2 N1 M0 non-small cell lung cancer

Thirty-four consecutive patients with non-small cell lung cancer plus N1 nodal metastases (eight with T1 N1 M0 and 26 with T2 N1 M0) were retrospectively reviewed. Nineteen had adenocarcinoma, 11 had squamous disease, and four had large cell carcinoma. Eleven patients had surgical resection alone (32.3%), with a median survival of 13 months. Seven patients (20.6%) had resection followed by radiation therapy, with a median survival of 19.2 months. Sixteen patients (47.1%) had resection followed by radiation therapy and chemotherapy, consisting of cyclophosphamide, doxorubicin, methotrexate, and procarbazine. Median survival for the latter group was 45.5 months, significantly greater than for those treated with resection alone (p less than 0.005). We did not observe any relationship between survival and age, cell type, number or location of diseased hilar nodes, distance of tumor from the resected bronchial margin, tumor size, the presence or absence of visceral pleural involvement, or the type of resection performed. Resection in combination with adjuvant radiation therapy and chemotherapy offers improved median survival over resection alone in patients with T1 N1 M0 and T2 N1 M0 non-small cell lung cancer.