Micrometastasis to axillary lymph nodes and bone marrow in breast cancer patients

The axillary lymph nodes of 100 lymph node-negative breast cancer patients with known bone marrow status have been re-examined to explore the presence of micrometastasis in lymph nodes and the covariance of micrometastasis to bone marrow and lymph nodes. Nodes were serially sectioned at three intervals of 100 microm, followed by immunohistological (two sections) and haematoxylin-eosin staining (one section). Tumours were mainly T1 and T2, and the patients had on average 13 (4-22) lymph nodes removed. In two patients, micrometastasis was detected in one node. Another 25 patients possessed single positive immunostained cells mimicking tumour cells. These cells have been shown to be false positive cells by Perl and melanin staining. One patient had metastasis to several nodes missed by the original examination. Immunocytochemical detection of micrometastasis in bone marrow revealed 11 marrow-positive patients. This study has identified a low frequency of micrometastasis to lymph nodes, and no covariance with micrometastasis in the bone marrow was seen. Bone marrow micrometastasis may be an independent prognostic variable, separate from axillary node status.     

Intrapulmonary lymph nodes enlarged after lobectomy for lung cancer

A 62-year-old man, who had had a left upper lobectomy for mucoepidermoid lung carcinoma, was admitted again 3 months later because of enlargement of four small nodules in the left lower lobe. A computed tomography–guided needle aspiration biopsy obtained insufficient material for diagnosis, and because pulmonary metastases were suspected, two of the four tumors were extirpated. Intraoperative frozen section found the nodules to be intrapulmonary lymph nodes. Intrapulmonary lymph nodes should be included in the differential diagnosis of coin lesions in the peripheral lung field.     

Mediastinoscopy in patients with clinical stage I non-small cell lung cancer

BACKGROUND: The aim of this study was to investigate the significance of mediastinoscopy for clinical stage I non-small cell lung cancer. METHODS: We reviewed 291 patients who underwent mediastinoscopy from January 1995 to December 2001 for clinical stage I non-small cell lung cancer. The patients who presented tumor-negative lymph nodes on mediastinoscopy underwent thoracotomy for pulmonary resection and mediastinal lymph node dissection in the same operative session. Mediastinoscopy-positive patients were referred for neoadjuvant therapy. RESULTS: Of the 291 patients, 20 patients (6.9%) were found with N2 or N3 disease on mediastinoscopy. Among 271 mediastinoscopy-negative patients, thoracotomy-proven N0 was found in 201 patients (74.2%), N1 in 44 patients (16.2%), and N2 in 25 patients (9.2%). Seventeen of 25 patients with unforeseen N2 disease had positive lymph nodes in the station that could be approached by mediastinoscopy only. The positive rate of mediastinoscopy was significantly higher in the patients with nonbronchioloalveolar-type adenocarcinoma than in squamous cell carcinoma (11.5% vs 3.3%, p = 0.013). However, there was no difference in the mediastinoscopy-positive rate between clinical T1 and T2 status. CONCLUSIONS: Though there are still controversies about routine mediastinoscopy in patients without mediastinal nodal enlargement on chest computed tomography scan, this study demonstrates that routine mediastinoscopy is necessary, especially for nonbronchioloalveolar-type adenocarcinoma patients.     

Segmental resection spares pulmonary function in patients with stage I lung cancer

Background

Segmental resection for stage I non-small cell lung cancer remains controversial. Reports suggest that segmentectomy confers no advantage in preserving lung function and compromises survival. This study was undertaken to assess the validity of those assertions.

Methods

We retrospectively analyzed patients undergoing lobectomy (n = 147) or segmentectomy (n = 54) for stage I non-small cell lung cancer between March 1996 and June 2001. All patients were included in the survival analysis. Pulmonary function testing was obtained preoperatively and at 1 year and included forced vital capacity, forced expiratory volume in 1 second, maximum voluntary ventilation, diffusing capacity, and stair-stepper exercise. Patients with recurrent disease (lobectomy, n = 32; segmentectomy, n = 10) were excluded in the pulmonary function testing analysis to avoid the confounding variables of tumor or treatments.

Results

Preoperative pulmonary function tests in segmentectomy patients were significantly reduced compared with lobectomy (forced expiratory volume in 1 second, 75.1% versus 55.3%; p < 0.001). At 1 year, lobectomy patients experienced significant declines in forced vital capacity (85.5% to 81.1%), forced expiratory volume in 1 second (75.1% to 66.7%), maximum voluntary ventilation (72.8% to 65.2%), and diffusing capacity (79.3% to 69.6%). In contrast, a decline in diffusing capacity was the only significant change seen after segmental resection. Oxygen saturations at rest and with exercise were maintained in both groups. Actuarial survival in both groups was similar (p = 0.406) with a 1-year survival of 95% for lobectomy and 92% for segmentectomy. Four-year survivals were 67% and 62%, respectively.

Conclusions

For patients with stage I non-small cell lung cancer, segmental resection offers preservation of pulmonary function compared with lobectomy and does not compromise survival. Segmentectomy should be considered whenever permitted by anatomic location.     

Imprint cytology for detecting metastasis of lung cancer in mediastinal lymph nodes

Background

Lymph node metastasis of lung cancer has been evaluated with histologic examination. We studied the usefulness of cytologic diagnosis for detecting metastasis of lung cancer in mediastinal nodes.

Methods

Five hundred twelve stations of mediastinal nodes in 157 patients with lung cancer were excised for staging of the disease through mediastinoscopy or thoracoscopy. Among them, 474 stations of mediastinal nodes in 151 patients were examined for metastasis both with imprint cytology and with hematoxylin-eosin histology independently. The final diagnostic decision was made by overall pathologic information, including cytology and histology. The diagnostic accuracies were compared between cytologic and histologic examinations.

Results

Cytologic examination identified 66 positive stations and 2 suspicious stations in 45 patients, whereas histologic examination identified 61 positive stations in 42 patients. The final pathologic diagnosis was 70 positive stations and 1 suspicious station in 45 patients. The sensitivity, accuracy, and negative predictive value of cytologic examination for node metastasis were 95.7%, 99.4%, and 99.3%, respectively, and those of histologic examination were 87.1%, 98.1%, and 97.7%, respectively. On a patient basis the sensitivity, accuracy, and negative predictive value of cytologic examination were 100%, 100%, and 100%, respectively, whereas those of histologic examination were 93.8%, 98.0%, and 97.2%, respectively. An additional 3 patients (2.0%) who had contralateral mediastinal node metastasis diagnosed only with cytology were identified with upstaged disease.

Conclusions

Imprint cytology for detecting metastasis of lung cancer in mediastinal nodes has high sensitivity and accuracy and is no less useful than histologic examination.     

Surgical assessment and intraoperative management of mediastinal lymph nodes in non-small cell lung cancer

Mediastinal lymph node status has important prognostic and therapeutic implications for nonsmall cell lung cancer patients. Consequently, an accurate pathologic assessment of mediastinal lymph nodes for metastasis is essential. Despite the significance of nodal assessment, practice patterns among surgeons vary widely. Therefore we reviewed the literature to provide evidence-based recommendations regarding the ideal means and extent of preoperative and intraoperative pathologic mediastinal lymph node staging in non-small cell lung cancer patients. We found that the most sensitive and accurate intraoperative method is a complete mediastinal lymph node dissection. Pathologic evaluation of at least 10 mediastinal lymph node from at least three stations should be performed at the time of surgery.     

Video-assisted thoracic surgery lobectomy for stage I lung cancer

BACKGROUND: The technique, safety, and oncologic efficacy of video-assisted thoracic surgery (VATS) lobectomy are controversial. Issues include operative time, lymph node yield, conversion to thoracotomy, resource utilization, recurrence, complications, and survival. METHODS: From January 1995 to December 2001, 179 patients underwent VATS lobectomy for preoperative stage I lung cancer (T1N0, 118 patients; T2N0, 61 patients). Mean age was 64.34 years (range, 38 to 87); 91 were female and 88 were male. Contraindications to VATS lobectomy included any suggestion of hilar, endobronchial, or central lesions. Video-assisted thoracic surgery lobectomy was performed using three ports, partial anatomic hilar dissection, and mediastinal node dissection. RESULTS: Distribution of lobectomies was as follows: left upper lobe, 50 patients; left lower lobe, 27 patients; right upper lobe, 33 patients; right upper and right middle lobe, 29 patients; right middle lobe, 9 patients; right lower lobe, 30 patients; right middle lobe and right lower lobe, 1 patient. Mean operative time was 75 +/- 6 minutes. Mean lymph node yield was 11 +/- 5 nodes. Pathologic upstaging was noted in 14 of the 179 patients (7.8%). Mean hospitalization was 4.1 days (range, 2 days to 4 months). There were no conversions to thoracotomy and there was 1 death (1 of 179, 0.05%). Complications included air leak in 24 of 179 (13.4%), subcutaneous emphysema in 4 of 179 (2.2%), pneumonia in 10 of 179 (5.6%), wound infection in 5 of 179 (2.8%), respiratory failure in 3 of 179 (1.7%), pulmonary embolism in 2 of 179 (1.1%), and myocardial infarction in 1 of 179 (0.5%). At a mean follow-up of 37 months, local recurrence rate was 0.013 per person per year. Actuarial recurrence-free survival was 88% and 85% at 36 and 60 months respectively. CONCLUSIONS: For carefully selected patients VATS lobectomy for early stage lung cancer is a safe and effective strategy. Long-term follow-up is required to fully evaluate recurrence and survival.     

The size of metastatic foci and lymph nodes yielding false-negative and false-positive lymph node staging with positron emission tomography in patients with lung cancer

BACKGROUND: We examined the sizes of lymph nodes and metastatic foci within the lymph nodes that affect false-positive and false-negative lymph node staging by positron emission tomography in lung cancer. METHODS: Preoperative positron emission tomography and computed tomography scans were performed for 564 lymph node stations in 80 patients with peripheral-type lung cancer. The sizes of both the lymph nodes and the metastatic foci within the lymph nodes were measured, and these measurements were compared with those obtained with positron emission tomography scanning. To establish general sizes of metastatic foci within the lymph nodes, 277 metastatic lymph nodes in operative specimens previously resected from another 111 patients with lung cancer were examined as a control. RESULTS: The sensitivity was significantly higher for positron emission tomography than for computed tomographic scanning (P =.026). The sizes of metastatic foci within lymph nodes that showed false-negative (n = 8) and true-positive (n = 28) with positron emission tomography ranged from 0.5 to 9 mm (3 +/- 1 mm) and from 4 to 18 mm (10 +/- 3 mm), respectively (P <.001). None of the metastatic foci smaller than 4 mm could be detected with positron emission tomography scanning. The review of the 277 previously resected metastatic lymph nodes showed that 89 (32%) had metastatic foci smaller than 4 mm. The sizes of true-positive (n = 28) and false-positive (n = 10) lymph nodes ranged from 6 to 15 mm (10 +/- 2 mm) and from 9 to 16 mm (12 +/- 2 mm), respectively (P <.01). None of the false-positive lymph nodes was smaller than 9 mm. CONCLUSIONS: Although positron emission tomography was superior to computed tomography scanning in lymph node staging in lung cancer, positron emission tomography was unable to distinguish metastatic foci smaller than 4 mm, which were not unusual sizes for lymph node metastases in lung cancer. Positive lymph nodes with positron emission tomography smaller than 9 mm are likely to be true-positive rather than false-positive.     

Risk factors influencing lymph nodes metastasis in lung cancer with stage I, II or IIIA

The purpose of this study was to assess the risk factors involved in the intrapulmonary, hilar and mediastinal lymph nodes metastases in seventy-eight patients with stage I, II or IIIA lung cancer postoperatively, which were resected from 1978 to 1988. In the histological type, the incidence of the mediastinal lymph nodes metastases in adenocarcinoma was higher than that in other types, such as squamous cell carcinoma and large cel carcinoma. In addition, the incidence of mediastinal lymph nodes metastases in the papillary type was significantly higher than that in the tubular type (p less than 0.05). The incidence of mediastinal lymph nodes metastases increased as invasion into the lymphatic duct and/or vessel was demonstrated (p less than 0.01, p less than 0.05). The proximal type, in which the cancer spread to the secondary segmental bronchus, metastasized to the hilar lymph nodes more frequently than the distal type, in which the cancer was located in the bronchus distal to the third segmental one. Although there was no significant relationship between the site of the cancer and the incidence of the metastatic lymph nodes, the hilar and superior mediastinal lymph nodes (#1-4, 3a, 3p) metastases were demonstrated regardless of the lobe in which the cancer was located. The primary tumor located in the left lower lobe of the lung tended to metastasize to the inferior mediastinal lymph nodes (#8, 9). Twenty-five out of 33 patients with the lymph nodes metastases had hilar metastatic lymph nodes. However, the mediastinal lymph nodes metastases were proved in 5 patients without any intrapulmonary and hilar lymph nodes metastases. No relationship between the histological differentiation, size of tumor, pT factor and the incidence of lymph nodes metastases was found.     

Serum carcinoembryonic antigen level in surgically resected clinical stage I patients with non-small cell lung cancer

BACKGROUND: There is little general agreement concerning the effectiveness of serum carcinoembryonic antigen (CEA) as a prognostic indicator for non-small cell lung cancer (NSCLC) in clinical stage I patients. We conducted a retrospective study to investigate the relationship between serum CEA level and survival. METHODS: We assessed 297 consecutive patients with clinical stage I NSCLC who underwent surgical resection at Toneyama National Hospital from 1985 to 1998. Serum CEA levels were measured with an enzyme-linked immunosorbent assay kit with the upper limit of normal defined as 7.0 ng/mL based on the 95% specificity level for benign lung disease, in our hospital. RESULTS: There were 56 (19%) patients with serum CEA greater than 7.0 ng/mL. The high CEA group had a median survival time of 50 months and a 5-year survival rate of 49% compared with a 5-year survival rate of 72% (p < 0.0001) for the normal CEA group (n = 241). Patients with postoperatively high CEA levels (n = 15) had the worse prognosis (median survival time 35 months, and 5-year survival 18%) compared with patients whose levels returned to normal (n = 41, median survival time 8.8 months, and 5-year survival 68%; p = 0.01). These differences were also observed in patients with pathologic stage I or II tumors but not in those with pathologic stage III or IV tumors. CONCLUSIONS: Serum CEA level is a useful predictor of survival for patients with clinical stage I NSCLC, and a persistently high CEA level after surgery is an especially strong indicator of a very poor prognosis.     

Thoracoscopic lobectomy: a safe and effective strategy for patients with stage I lung cancer

BACKGROUND: Thoracoscopic lobectomy is emerging as a potential alternative to thoracotomy for early stage lung cancer. The issues of safety and oncologic efficacy should be analyzed before recommending this procedure for widespread use. METHODS: Thoracoscopic lobectomy was attempted in 110 consecutive patients (age, 35 to 81 years) with tumors that were judged to be amenable to lobectomy over a 26-month period. Exclusion criteria included tumors greater than 5 cm in diameter, T3 tumors, endobronchial tumors visible at bronchoscopy, the use of induction therapy, extensive N1 disease on computed tomographic scan, and N2 disease at mediastinoscopy. The procedures were performed without rib spreading using two ports and included anatomic hilar dissection and individual vessel stapling. RESULTS: Thoracoscopic lobectomy and mediastinal lymph dissection was successfully performed in 108 patients (98.2%); 2 patients required conversion to thoracotomy to control bleeding in the setting of dense hilar adenopathy. There were no intraoperative deaths and 4 perioperative deaths (3.6%) caused by pneumonia and associated adult respiratory distress syndrome (3 patients) and stroke (1 patient). Major complications included pneumonia (5 patients), stroke (1 patient), and return to the operating room to revise the bronchial closure (1 patient). Minor complications included prolonged air leak (6 patients), atrial fibrillation (4 patients), blood transfusion (2 patients) and ileus (1 patient). Median time to chest tube removal was 3 days, and median length of stay was 3 days. CONCLUSIONS: Thoracoscopic lobectomy is a safe and effective strategy for patients with early stage lung cancer. Long-term follow-up is required to determine if recurrence rate and 5-year survival are comparable with thoracotomy for lobectomy.     

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.