Histogram analysis of computed tomography numbers of clinical T1 N0 M0 lung adenocarcinoma, with special reference to lymph node metastasis and tumor invasiveness

PURPOSE: To predict lymph node metastasis and tumor invasiveness in lung adenocarcinoma from computed tomography findings, we examined computed tomography number histograms of clinical T1 N0 M0 lung adenocarcinomas. PATIENTS AND METHODS: Histograms of pixel computed tomography numbers were made for 100 patients with clinical T1 N0 M0 lung adenocarcinoma. Pathological tumor stages were N0 in 80 patients, N1 in 7, N2 in 9, and T4 due to intrapulmonary metastasis in 4. RESULTS: The histogram showed 3 patterns: 1 peak at a low computed tomography number (n = 18), 1 peak at a high computed tomography number (n = 54), and 2 peaks at both low and high computed tomography numbers (n = 28). Histologically, adenocarcinoma with 1 peak at a low computed tomography number showed a large area of bronchioloalveolar carcinoma-like spread with little area of solid growing tumor or central fibrosis, whereas those with 1 peak at a high computed tomography number showed a large area of solid growing tumor or central fibrosis with little bronchioloalveolar carcinoma-like spread. Adenocarcinomas with 2 peaks had both types of areas. Lymph node or pulmonary metastases were seen in none (0%) of the adenocarcinomas with 1 peak at a low computed tomography number, in 1 (4%) with 2 peaks, and in 20 (37%) with 1 peak at a high computed tomography number. The former 2 types had metastases less frequently than those with 1 peak at a high computed tomography number (P <.01). In the 79 patients with pathological T1 N0 M0, tumor involvement of the intratumoral vessels or pleura was seen in 1 of 18 (6%) adenocarcinomas with 1 peak at a low computed tomography number, which was significantly less frequent than the 18 of 34 (53%) with 1 peak at a high computed tomography number (P <.001) and 10 of 27 (37%) with 2 peaks (P <.05). CONCLUSION: Clinical T1 N0 M0 adenocarcinomas with 1 peak at a low computed tomography number on histogram seldom had lymph node metastasis or tumor involvement of vessels or pleura. Limited surgical resection could be indicated for this type of adenocarcinoma, especially for elderly patients or patients with poor pulmonary function.     

Immunohistochemically detected micrometastases in peribronchial and mediastinal lymph nodes from patients with T1, N0, M0 pulmonary adenocarcinomas

The T1, N0, M0 subset of stage I lung adenocarcinoma is a tumor that has a 5-year disease-free survival rate of 66% to 85%. To date, there has not been a rigorous immunohistochemically detected lymph node micrometastasis study composed of patients with identical stage and type of tumors, and in which standard histologic features were incorporated into multivariate analyses. We immunohistochemically examined the peribronchial and mediastinal lymph nodes from 80 consecutively accrued patients with T1, N0, M0 adenocarcinomas and bronchioloalveolar carcinomas unselected for distant metastasis, and an additional 39 patients with similar stage and type neoplasms who were selected for their development of metastases to evaluate the prevalence of micrometastases, their association with distant metastases, and their relationship with other pathologic prognostic features. All slides were stained with keratin AE1/3. Micrometastases were confirmed with Ber-Ep4. Three immunohistochemically detected lymph node micrometastases were identified in three of 80 consecutively accrued patients (4%). These three positive stains constituted 0.5% of the 573 stains required to immunohistochemically screen all of the lymph node blocks from these patients. Among the 39 patients who were selected because they developed distant metastases, three immunohistochemically detected lymph node micrometastases from three patients were identified, which constituted 8% of patients in this group and 1% of the 280 stains required to screen all of these patients' lymph nodes. Small vessel invasion, maximum tumor dimension, and immunohistochemically detected lymph node micrometastases were independently associated with metastases on multivariate analysis. Among patients who developed metastases, there was no significant difference in the disease-free survival rate between those with and those without immunohistochemically detected lymph node micrometastases. Given the low sensitivity in terms of the number of immunohistochemical stains performed, and the prognostic significance of standard histologic features, the use of immunohistochemical screening lymph nodes from all patients with T1, N0, M0 adenocarcinomas is questionable.     

临床T1、T2 N0 M0乳腺癌腋窝淋巴结转移状况研究的意义

目的 探讨临床T1、T2、 N0、M0.乳腺癌腋窝淋巴结转移状况及临床意义.方法 结合原发肿瘤位置、年龄、病理等,分析了276例临床T1、T2 N0M0乳腺癌患者腋窝淋巴结转移情况及意义.结果 临床T1 N0M0.腋淋巴结转移率低于T2 N0M0乳腺癌患者(P=0.027),乳腺中央区与外下象限乳腺癌发生腋淋巴结转移明显高于其他部位肿瘤(P=0.004);乳腺外侧象限肿瘤腋窝下组淋巴结转移率高于其他部位肿瘤组(P=0.000);乳头中央区和内侧象限乳腺癌腋上组淋巴结转移高于乳腺外侧象限肿瘤(P=0.000).非特殊型癌发生淋巴结转移明显高于早期癌和其他类型(P-0.001).9例单纯癌6例发生2组以上腋淋巴结转移.90例发生腋淋巴结转移的病例中,>50岁者62例(68.9%)发生腋淋巴结转移,≤50岁者28例(31.1%)发生腋淋巴结转移(P=0·000).发现"跳跃式"转移病例2例(0.7%),均为临床T2 N0M0患者,肿瘤位于乳头中央区1例,外下象限者1例.其中浸润型导管癌1例,单纯癌1例.结论 研究临床T1、T2 N0M0乳腺癌腋窝转移淋巴结分布情况对开展SLNB及制定合理的治疗方案有一定指导价值.     

Refining esophageal cancer staging

OBJECTIVE: Cancer staging is dynamic, reflecting accrual of knowledge and experience in treatment. The objectives of this study were to assess current esophageal cancer staging and to determine whether refinements of classification and stage grouping are necessary. METHODS: From 1983 through November 2000, 480 patients underwent esophagectomy without induction therapy. Depth of tumor invasion (T), regional lymph node status (N), distant status (M), number of metastatic regional lymph nodes, and histopathologic type and grade were subjected to survival-tree analysis, multivariable Cox and hazard function analysis, and residual misclassification risk analysis. RESULTS: Inhomogenity of survival was found within and lack of distinction was found between current American Joint Committee on Cancer staging groups, supporting the need for refinement. T1 and N1 were redefined on the basis of survival differences. T1a is intramucosal cancer, T1b is submucosal cancer (P =.008), N1 is 1 or 2 metastatic regional lymph nodes, and N2 is 3 or more metastatic regional lymph nodes (P =.01). Current subclassification of M1 is not warranted (P =.9). Histopathologic type (P =.17) and grade (P =.3) minimally refined staging. Reassignment of staging groups constrained by American Joint Committee on Cancer definitions of stages 0 and IV produced less monotonic, distinctive, and homogeneous survival than free assignment of staging groups. CONCLUSIONS: Current American Joint Committee on Cancer staging of esophageal cancer is inadequate. Refinement requires redefinition of T1, N1, and M1 classifications. Stage grouping within the constraints of American Joint Committee on Cancer definitions produces less accurate prognosis than free assignment based on survival data.     

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.     

Prognosis in stage II (T1N1M0) breast cancer.

As part of a detailed study of prognostic factors in breast cancer, we have analyzed the ten year survival rates of 524 patients with primary invasive carcinomas 2.0 cm or less in diameter (T1). This report describes the subset of 142 patients (27%) who had metastases only in axillary lymph nodes (T1N1M0). All the patients were treated initially by at least a modified radical mastectomy. Factors associated with a significantly poorer prognosis were: axillary lymph node metastases suspected on clinical examination; perimenopausal menstrual status at diagnosis; tumor larger than 1.0 cm; prominent lymphoid reaction; infiltrating duct or lobular rather than medullary, colloid and tubular carcinoma; and blood vessel invasion. When compared with those patients with negative nodes (T1N0M0), the patients with one or more lymph node metastases had a significantly poorer prognosis. Generally, survival rates tended to diminish as the number of involved lymph nodes increased. In this respect, comparison of patients with one-three and four or more nodal metastases provided a significant discrimination of prognostic groups in the entire series. However, for patients with disease limited to Level I, the same discrimination was obtained comparing those with one-two and three or more positive nodes. In the subset with a single lymph node metastasis, the size of the metastasis (micro or less than or equal to 2 mm vs macro or greater than 2 mm) was not significantly related to prognosis. Lymph node metastases were significantly less frequent among tumors smaller than 1 cm and special tumor types (medullary, colloid, lobular and tubular). However, no factor proved to be a reliable predictor of the presence of axillary metastases for the single largest group consisting of patients with infiltrating duct carcinoma 1-2 cm in diameter.     

Renal cell carcinoma with extension of tumor thrombus into the vena cava: surgical strategy and prognosis

PURPOSE: The outcome of patients who underwent radical resection of renal cell carcinoma extending into the vena cava was retrospectively analyzed, and risk factors for long-term survival were investigated. METHODS: From 1983 to 1999, 33 patients who had renal cell carcinoma with inferior vena caval tumor extension underwent 34 surgical procedures. There were 27 men and six women with an average age of 60.1 years. Twenty-two cases (64.7%) were classified as stage III (T1-2 N1 M0 or T3 N0-1 M0), and 12 cases (35.3%) as stage IV (T4 or N2-3 or M1). Coexistent lung metastasis was found in seven cases (20.6%). The tumor thrombi invaded into the inferior vena cava below the hepatic hilum in 19 cases, below the orifice of hepatic veins in 12, and above the diaphragm in 3. Cardiopulmonary bypass graft was applied in 13 cases (38.2%). Inferior vena cava was reconstructed by direct suture (n = 19), polytetrafluoroethylene patch angioplasty (n = 13), or graft replacement (n = 2). RESULTS: Two patients died during the early postoperative period because of retrohepatic caval injury and intraoperative pulmonary embolism. Late death occurred in 16 patients; the causes of death were tumor recurrence in 15 and acute pulmonary embolism as a result of graft thrombosis in 1. Overall 1-, 5-, and 10-year survival rates were 70%, 44%, and 26.4%, respectively. One- and 5-year survival rates were 81.3% and 52.9% for stage III and 50% and 31.2% for stage IV; a statistically significant correlation was found between surgical staging and survival (P =.049). Patients without lymph node metastasis had a significant survival advantage over those with lymph node metastasis (P =.022). There was no significant difference in survival on the basis of the presence or absence of synchronous lung metastasis (P =.291). The degree of local extension of the tumor or the level of tumor thrombus did not tend to influence survival. CONCLUSIONS: Surgical prognosis in patients with renal cell carcinoma extending into the vena cava was determined by the staging of the tumor, especially lymph node status, and not by the level of tumor thrombus or the presence of concurrent lung metastasis. The use of cardiopulmonary bypass graft is recommended for the resection of tumor thrombus extending over the diaphragm.     

Proportion of ground-glass opacity on high-resolution computed tomography in clinical T1 N0 M0 adenocarcinoma of the lung: A predictor of lymph node metastasis

OBJECTIVE: In patients with clinical T1 N0 M0 lung adenocarcinoma, we investigated whether the proportion of ground-glass opacity area measured on high-resolution computed tomography was valuable for predicting the existence of lymph node metastasis, lymphatic invasion, or vascular invasion. METHODS: Between 1994 and 1999, 111 patients with clinical stage IA adenocarcinoma underwent surgical resection of the lung at our hospital. Of these, 96 patients received high-resolution computed tomography of the chest, and they constituted the study population. The tumors were semiquantitatively classified into 5 groups on the basis of the proportion of ground-glass opacity area to whole tumor shadow on high-resolution computed tomography: group I, 0%; group II, 1% to 25%; group III, 26% to 50%; group IV, 51% to 75%; and group V, 76% to 100%. Correlations of computed tomographic findings, pathologic results of lymph node metastasis and lymphatic and vascular invasion, and the histologic subtype according to the new World Health Organization classification were examined. We also investigated the characteristics of the patients with ground-glass opacity areas on high-resolution computed tomography and their value for predicting lymph node metastasis. RESULTS: Among the 96 patients, 15 (15.6%) had mediastinal lymph node metastases, and 3 (3.1%) had hilar node metastases. Regarding the proportion of the ground-glass opacity area of the tumors, 15 (15.6%) tumors were classified as group V, 11 (11.5%) as group IV, 9 (9.3%) as group III, 22 (22.9%) as group II, and 39 (40.6%) as group I, respectively. Of the 18 patients with lymph node metastases, no patients were found in groups IV and V, 2 (22.2%) were found in group III, 4 (18.2%) were found in group II, and 12 (30.8%) were found in group I (trend P =. 003), respectively. Twenty-six patients classified into groups IV and V also showed neither lymphatic invasion nor recurrence. All the smaller tumors (< or =2.0 cm) in group IV or V were histologically proved to be bronchioloalveolar carcinoma. Adjusted for smoking status and other characteristics, patients without ground-glass opacity on high-resolution computed tomography had a significantly increased risk of concurrent lymph node metastasis compared with those with ground-glass opacity. CONCLUSION: In patients with clinical T1 N0 M0 adenocarcinoma, the proportion of ground-glass opacity area on thin-section computed tomography scans was a strong predictor for tumor aggressiveness and thus could be a useful index for planning limited surgical resection for these patients.     

Effect of radioisotope sentinel node mapping in patients with cT1 N0 M0 lung cancer

BACKGROUND: Application of the sentinel node concept to lung cancer is still controversial. Patients with peripheral small lung cancers would gain the most benefit from this concept, if it were valid. We sought to determine whether it is possible to choose between limited lymph node sampling and systematic lymphadenectomy from the distribution of sentinel lymph nodes in patients with node-negative disease on the basis of imaging. METHODS: Sixty-five consecutive patients with cT1 N0 M0 non-small cell lung cancer were enrolled. A radioisotope tracer (4 mCi of technetium-99m tin colloid, 2.0 mL) was injected in the vicinity of the tumor before surgical intervention with computed tomographic guidance. The radioactivity of each resected lymph node was measured separately with a hand-held gamma probe after complete tumor resection. Sentinel nodes were identified, and the accuracy of sentinel node mapping was examined. Whether the location of the sentinel node depended on the site of the primary tumor was also examined. RESULTS: Of the 65 patients, 3 were excluded because of the final pathologic results. Successful radionuclide migration occurred in 39 (62.9%) of the 62 patients. There was 1 (2.6%) false-negative result among 39 patients with a sentinel node, and therefore the sensitivity was 90%, and the specificity was 100%. The most common sentinel lymph nodes were at level 12 (46.7%), followed by level 11 (18.3%), the mediastinum (16.7%), and level 10 (11.7%). CONCLUSION: The sentinel node concept is valid in patients with cT1 N0 M0 lung cancer. The lobar lymph nodes were identified as sentinel nodes more frequently than other lymph nodes. We need to make further efforts to increase the sentinel node identification rate. However, we believe that if sentinel nodes are identified, sentinel node mapping can allow the accurate intraoperative diagnosis of pathologic N0 status in patients with cT1 N0 M0 lung cancer.     

EMA在pT1-3N0胃癌淋巴结微转移检测中的意义

目的pT1-3N0期胃癌术后临床病理因素（性别、年龄、肿瘤部位、肿瘤直径、大体分型、浸润胃壁深度、分化程度、血管侵润和淋巴管浸润）和淋巴结微转移对术后5年无瘤生存率的影响。方法纳入研究对象为pT1-3N0期胃癌共有108例,均为胃肠组医师行胃癌根治术。术后平均随访65.12个月（22～120个月）,每位患者淋巴结9枚至28枚不等,将所有淋巴结用EMA指标进行免疫组化染色。临床病理因素及微转移对5年无瘤生存率的影响进行统计分析。结果“肿瘤直径”（P=0.033）,“浸润胃壁深度”（P=0.024）和“是否有淋巴管浸润”（P=0.005）与淋巴结的上皮膜抗原（EMA）表达有正相关性,而其他临床病理因素与淋巴结EMA表达无明显相关性。临床病理因素对5年无瘤生存率无明显影响。淋巴结EMA表达阴性,孤立肿瘤细胞巢（Isolated Tumor Cells,ITCs）和微转移（Micrometastasis,MCM）的患者,5年无瘤生存率分别为88.50%,75.60%和44.40%。ITCs与EMA（-）的患者5年无瘤生存率无显著差别（P=0.360）,而MCM与EMA（-）的患者5年无瘤生存率出现明显差别（P=0.002）。结论对于pT1-3N0期胃癌,若淋巴结中检测出微转移,其预后较差,术后复发率较高,术后应予以积极的辅助治疗。     

T1、T2肺鳞癌及腺癌淋巴结转移特点及其临床意义

目的 研究Ｔ１、Ｔ２肺鳞及腺癌淋巴结转移频度、分布范围及特点,为广泛清扫提供依据。方法 按Ｎａｒｕｋｅ肺癌淋巴结分布图对２５４例Ｔ１、Ｔ２肺鳞癌及腺癌施行了手术切除及广泛肺内、叶间及纵阴淋巴结清扫术并对其进行统计分析。结果 清除淋巴结１６８５组。Ｎ１淋巴结转移率２０．０％,Ｎ２淋巴结转移率为１０．２％。Ｔ１、Ｔ２间淋巴结转移率差异有非常显著性意义（Ｐ〈０．０１）。Ｔ１鳞癌无Ｎ２转移,Ｎ２转移在鳞癌     

Surgical indication of T1-2N2-3M0 lung cancer based on the prognosis

Effusion-type lung cancer with postoperative T1N2-3M0 and primary tumor diameter less than 3 cm was regarded as small sized progressive lung cancer. There were 8 cases of pT1N2-3, with a 3-years survival rate of 37.5%, and, 5 years survival rate of 25.0%. There were 5 cases of effusion-type lung cancer with primary tumor diameter less than 3 cm, who were treated with panpleuropneumonectomy. Their 3 years survival rate was 51.9%. In small sized progressive lung cancer in total, the 3 years survival rate was 40.7%, and the 5 years survival rate was 29.1%. In comparison there were 29 cases of pT2N2-3, with a 3 years survival rate of 40.9% and a 5 years survival rate of 37.0%. There was no significant difference concerning the survival rate between T1 and T2 groups, T2 and pleuropneumonectomy group, and between small progressive lung cancer group and T2 group. Therefore, there seems to be a less correlation between progressive lung cancer and T-factor disease prognosis. It was suggested to improve the prognosis by extending lymph node dissection even in progressive lung cancer.     

Neoadjuvant therapy in non-small cell lung cancer. Prognostic impact of "mediastinal downstaging"]

In the course of a prospective multicenter study, 40 (26 squamous cell and 14 adenocarcinomas) patients with stage IIIA and IIIB non-small cell lung cancer (NSCLC) were submitted to surgery after neoadjuvant radiochemotherapy. Pretherapeutic clinical lymph node status was compared to the lymph node involvement established in the resection specimens. Therapy-induced tumor regression was classified according to a three-step tumor regression grading system. In 29 patients (72.5%) a downward shift in lymph node involvement could be established,whereas in 27.5% ( n=11) pretherapeutic lymph node status was maintained. Of 26 patients with post-therapeutic N0 or N1 status, 21 revealed less than 10% vital tumor tissue in the resection specimens (regression grades IIb or III). Patients with post-therapeutic N0 or N1 lymph node status were found to have a survival benefit compared to patients with N2 lymph node involvement, though this difference was not statistically significant (p=0.27). On the other hand, tumor regression showed a significant correlation to the overall survival period (p=0.02). Thus, therapy-induced tumor regression grading seems to be a more precise method to predict the outcome of the disease.     

Correlation between computed tomographic findings, bronchioloalveolar carcinoma component, and biologic behavior of small-sized lung adenocarcinomas

OBJECTIVE: Differentiation of bronchioloalveolar carcinoma from other subtypes of lung adenocarcinomas is important in the preoperative assessment of patients. We examined the biologic aggressiveness of small-sized adenocarcinomas according to the pathologically defined bronchioloalveolar carcinoma degree and its correlation with computed tomography findings. In addition, we attempted to predict which patients were suitable for a lesser resection. METHODS: Of 424 consecutive patients who underwent operation for primary lung cancer in the last 3 years, 114 with a histopathologically proven adenocarcinoma 3 cm or less in diameter underwent complete removal of the primary tumor. We examined the characteristics of patients classified into 3 groups based on the proportion of the bronchioloalveolar carcinoma component: 0% to 20% (n = 40), 21% to 50% (n = 38), and 51% to 100% (n = 36). We also investigated the correlation of the bronchioloalveolar carcinoma component with computed tomography findings such as ground-glass opacity (defined as a hazy increase on the lung window) and tumor shadow disappearance rate (defined as the ratio of the tumor area of the mediastinal window to that of the lung window). RESULTS: Male gender (P =.0001), advanced pathologic stage (P =.001), larger size of the tumor (P =.004), nodal involvement (P =.04), pleural invasion (P =.0003), lymphatic invasion (P =.002), and vascular invasion (P =.0002) were observed more often among patients with a smaller proportion of bronchioloalveolar carcinoma. A positive and significant correlation was found between the rate of bronchioloalveolar carcinoma component and ground-glass opacity (R(2) = 0.488, P <.0001) and tumor shadow disappearance rate (R(2) = 0.727, P <.0001). As an independent predictor of nodal status, tumor shadow disappearance rate (P =.015) and bronchioloalveolar carcinoma component (P =.015), as well as tumor size, were significantly valuable, although ground-glass opacity proportion (P =.086) was marginally informative. CONCLUSIONS: Small-sized adenocarcinomas with a greater ratio of bronchioloalveolar carcinoma component showed less aggressive behavior. Both tumor shadow disappearance rate and ground-glass opacity ratios, which are obtained preoperatively, were well associated with bronchioloalveolar carcinoma ratios, which are determined postoperatively. Furthermore, tumor shadow disappearance rate had a stronger impact as a predictor of bronchioloalveolar carcinoma component. Preoperative assessment of tumor shadow disappearance rate may be useful to identify patients requiring a less extensive pulmonary resection.     

Pathologic N1 non-small cell lung cancer: correlation between pattern of lymphatic spread and prognosis

OBJECTIVES: Patients with N1 non-small cell lung cancer represent a heterogeneous population with varying long-term survivals. Prognosis and pattern of recurrence seem to be particularly affected by the level of lymph node involvement. METHODS: From 1990 to 1995, a total of 1954 consecutive patients underwent surgical resection for non-small cell lung cancer: 549 (28%) had ipsilateral pulmonary lymph node metastases (N1). The hospital survivors (n = 535) were reviewed. Three levels of lymph node metastases (hilar, interlobar, and lobar) were identified according to the new Regional Lymph Node Classification for Lung Cancer Staging and differentiated from lymph node involvement on the basis of direct invasion. RESULTS: 1 The overall 5-year survival of patients with N1 disease was 40%. Survival was related in the univariate analysis to T classification, level-type of N1 involvement, number of involved nodes, multilevel involvement, Karnofsky Index, R status, and adjuvant therapy. In the multivariate analysis, only T classification and level-type of N1 involvement clearly showed statistical power (P =.000 and P =.001, respectively). The pattern of cancer relapse according to level-type of N1 involvement differed significantly: hilar N1 disease recurred at distant sites in 41% of patients and locoregionally in 12% of patients, whereas N1 disease by direct invasion occurred in 24% and 17% of patients, respectively (P =.030). CONCLUSIONS: Metastases to ipsilateral hilar, interlobar, or both, lymph nodes are associated with a poorer prognosis compared with metastases in intralobar lymph nodes or with lymph node involvement by means of direct invasion. Although surgical resection remains the mainstay of treatment, the high rate of tumor recurrence in both groups mandates further randomized studies with multimodality therapy approaches.     

Modified stage I (T1N0M0, T2N0M0), nonsmall cell lung cancer: treatment results, recurrence patterns, and adjuvant immunotherapy

We analyzed 96 patients who had surgery with T1N0M0 or T2N0M0 nonsmall cell lung cancer (NSCLC) to identify survival rates and recurrence patterns in well-staged patients and to evaluate adjuvant therapy. Preoperative staging included chest x-ray, gallium 67 scanning, and bronchoscopy in all patients. At thoracotomy, multiple mediastinal lymph node sites were routinely sampled. The results included an operative mortality rate of 5.2%, and the actuarial 5-year survival rate of all patients was 70.0%. Survival of T1N0 (n = 44) and T2N0 (n = 47) patients was 72.1% and 68.3%, respectively (p = NS). Survival was not affected by type of surgery, cell type, sex, age, or race. Late death was due to recurrence in 12 patients, a new airway malignancy in three, and a noncancer problem in six. Disease recurred in 15 patients: four (9.1%) T1N0 patients versus 11 (23.4%) T2N0 patients, p less than 0.05. Recurrence was local in four patients and distant in 11. Second lung cancers developed in six patients at a mean interval of 65.7 months after resection. A prospective, randomized trial of systemic immunotherapy with bacillus Calmette-Guerin (BCG) skin scarification was carried out in 29 patients. Survival in those patients receiving BCG was 85.9% compared with 63.9% for control subjects (p = 0.075) and 69.6% for patients not in the study (p = 0.077). The following conclusions can be made: Resection for well-staged, modified stage I NSCLC results in a 5-year survival rate of 70%. Nearly half the deaths are unrelated to recurrence of the original cancer. Recurrences are more frequent in T2N0 patients, but there is no survival difference compared with T1N0 patients. Systemic recurrences are more frequent than local recurrences, and there is an appreciable incidence of second lung cancers. Adjuvant chemotherapy or radiation therapy does not seem justified, but systemic immunotherapy holds sufficient promise to warrant further investigation.     

Neoadjuvante Therapie des nichtkleinzelligen Lungenkarzinoms

In the course of a prospective multicenter study, 40 (26 squamous cell and 14 adenocarcinomas) patients with stage IIIA and IIIB non-small cell lung cancer (NSCLC) were submitted to surgery after neoadjuvant radiochemotherapy.Pretherapeutic clinical lymph node status was compared to the lymph node involvement established in the resection specimens.Therapy-induced tumor regression was classified according to a three-step tumor regression grading system.In 29 patients (72.5%) a downward shift in lymph node involvement could be established,whereas in 27.5% (n=11) pretherapeutic lymph node status was maintained.Of 26 patients with posttherapeutic N0 or N1 status, 21 revealed less than 10% vital tumor tissue in the resection specimens (regression grades IIb or III).Patients with posttherapeutic N0 or N1 lymph node status were found to have a survival benefit compared to patients with N2 lymph node involvement, though this difference was not statistically significant (p=0.27). On the other hand, tumor regression showed a significant correlation to the overall survival period (p=0.02).Thus, therapy-induced tumor regression grading seems to be a more precise method to predict the outcome of the disease.     

Prognosis and histologic features of small pulmonary adenocarcinoma based on serum carcinoembryonic antigen level and computed tomographic findings.

OBJECTIVES: In 2001, we proposed the criteria for combined evaluation of the serum carcinoembryonic antigen (CEA) level and the tumor shadow disappearance rate (TDR) to predict pathologic N0 (pN0) disease in pulmonary adenocarcinomas. The objective of the present study was to determine the prognosis and histologic features in small-sized pulmonary adenocarcinomas according to serum CEA level and TDR. METHODS: We reviewed clinical records of 189 consecutive patients with peripheral pulmonary adenocarcinoma 3.0 cm or smaller who underwent major lung resection and systematic lymph node dissection: 50 patients with TDR 0.8 or more and normal CEA level (group I) and 139 patients with TDR <0.8 and/or elevated CEA level (group II). Among them, we investigated histologic features of 177 adenocarcinomas according to serum CEA level and TDR. RESULTS: The 5-year survival rates were 95% for group I and 75% for group II (P = 0.002) and for pN0 patients, 97% in group I and 87% in group II (P = 0.04). In univariate analyses, TDR, preoperative serum CEA level, and the maximum tumor dimension on computed tomographic (CT) scan were significantly associated with prognosis. Multivariate analysis showed that only preoperative serum CEA level and TDR were significant independent prognostic factors, and the maximum tumor dimension was not significant. Group I patients developed no local recurrence, including lymph node metastases. In 25 group I adenocarcinomas 2.0 cm or smaller, no lymph node involvement, two lymphatic permeation, two vascular invasion, and one pleural involvement tumors were observed. These signs of local invasiveness were less frequent than the remaining adenocarcinomas. CT findings correlated well with histologic findings in small-sized adenocarcinomas. CONCLUSIONS: Combined evaluation of preoperative serum CEA level and TDR may enable us to identify minimally invasive adenocarcinomas with good prognosis. Candidates for limited lung resection without systematic lymph node dissection could be selected based on these findings.     

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.     

Role of axillary node dissection in patients with T1a and T1b breast cancer: Mayo Clinic experience.

HYPOTHESIS: The incidence of nodal positivity in patients with early breast cancer is low, and axillary lymph node dissection may not be justified in all such patients. DESIGN: Retrospective case series. SETTING: Tertiary institution. PATIENTS: All patients with T1a and T1b breast cancer who had both primary breast surgery and axillary lymph node dissection at Mayo Clinic in Jacksonville, Fla, from January 1, 1992, through February 28, 1998. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Tumor size and biological grade, estrogen and progesterone receptor status, number of nodes harvested, and number of nodes positive for disease. RESULTS: Of 163 patients studied, 39 had T1a and 124 had T1b tumors. Node positivity was 0% for T1a and 11.3% for T1b tumors (P =.03). Lymph node involvement and estrogen receptor status were not related (P =.29). However, the risk of lymph node positivity for progesterone receptor-negative (P =.01) and estrogen receptor-negative/progesterone receptor-negative tumors was significantly higher than for progesterone and estrogen/progesterone receptor-positive tumors (P =.04). Furthermore, the risk of lymph node positivity was significantly higher as tumor size increased (P =.002). Finally, higher tumor grade conferred a higher risk of lymph node involvement (P =.02). CONCLUSIONS: T1a tumors have minimal risk of nodal positivity and may not require subsequent axillary lymph node dissection in the future. T1b tumors should be managed with routine analysis of axillary lymph node status. Whether sentinel node mapping can change this standard awaits further study.