Faculty Bibliography

BACKGROUND: Positron emission tomography (PET) scans often help direct biopsies of mediastinal lymph nodes in patients with non-small cell lung cancer (NSCLC), but the maximum standard uptake value (maxSUV) of individual nodes has not been evaluated. METHODS: This is a prospective study of consecutive patients with NSCLC, all of whom underwent integrated fluorodeoxyglucose-positron emission-computed tomography (FDG-PET-CT) and had biopsy or resection of their mediastinal lymph nodes. RESULTS: There were 397 patients. One-hundred and forty-three patients had N2 disease and 1,252 N2 nodes were pathologically examined. The median maxSUV of the nodes that had metastatic disease were the following: for the 2R node, 10.4 (range, 0-18.6); for 4R, 8.6 (range, 0-18.3); for 5, 8.9 (range, 0-26.3); for 6, 7.6 (range, 0-19.6); for 7, 7.7 (range, 0-14); for 8 and 9, 5.4 (range, 0-8.9). The median maxSUV for all of the N2 nodes that were benign was 0 (range, 0-18.8) (p < 0.05 for all stations except for nodes 8 and 9). When a maxSUV of 5.3 is used the accuracy of integrated FDG-PET-CT for each N2 nodal station is maximized and is at least 92% for each. CONCLUSIONS: The maxSUV of individual mediastinal lymph nodes is a predictor of malignancy. There is overlap between false and true positives. Definitive biopsies are required to prove cancer irrespective of the maxSUV value. However, when a maxSUV of 5.3 is used instead of the traditional value of 2.5, the accuracy for FDG-PET-CT for each N2 nodal station increases to at least 92%.

BACKGROUND: The stage of esophageal cancer is currently determined by the anatomic TNM classification system as opposed to information about tumor biology. METHODS: A retrospective review was made of a prospective electronic database. Patients had esophageal cancer, dedicated positron emission tomography (PET) using F-18-fluorodeoxyglucose (FDG-PET) and maximum standardized uptake value (maxSUV) measured. Biopsies were obtained from suspicious nodal and systemic locations, and when indicated, resection with complete lymphadenectomy was performed. RESULTS: There were 89 patients (53 men). The median maxSUV for patients with high grade dysplasia, stage I, IIa, IIb, III, and IVa esophageal cancer was 1.7, 2.9, 8.9, 7.7, 9.5, and 12, respectively. Multivariate analysis showed patients with a high maxSUV were more likely to have poorly differentiated tumors (risk ratio 1.89, p = 0.032) and advanced stage (risk ratio 2.6, p < 0.001). The maxSUV correlated better (r(2) = 0.85) than the current TNM staging system for survival (r(2) = 0.68). Receiving operator characteristics curve demonstrated a maxSUV of 6.6 to be the optimal cut-off point. The 4-year survival of patients with a maxSUV of 6.6 or less was 89%, whereas it was only 31% for those patients with values greater than 6.6 (p < 0.001). CONCLUSIONS: The maxSUV of an esophageal cancer on dedicated FDG-PET scan is an independent predictor of stage, tumor characteristics, and survival. It predicts survival better than the current TNM staging system. This information may help guide treatment strategies.

BACKGROUND: Despite the use of integrated positron emission tomography and computed tomography scans in patients with nonsmall-cell lung cancer, N2 disease is often missed. Knowledge of the N2 station most likely to be malignant based on the lobar location of the primary may help guide biopsies. METHODS: A retrospective review of an electronic prospective database of patients with nonsmall-cell lung cancer who underwent positron emission tomography and computed tomography clinical staging and had nodal biopsy or resection with complete lymphadenectomy, or both. RESULTS: The incidence and location of N2 disease of the 954 patients based on the location of the primary tumor was as follows: for right upper lobe cancers, 27% had N2 disease, most commonly in the 4R (23%); right middle lobe, 15%, most commonly in the 4R (8%) and the 7th station (6%); right lower lobe, 30%, most commonly in the 4R (15%) and the 7th station (14%); left upper lobe, 20%, most commonly in the 6 (16%); and left lower lobe, 22%, most commonly in the 7 (8%). Patients with right middle lobe cancer were more likely to have N1 disease (p = 0.014). Skip metastases (no N1, but N2 disease) was most common with left upper lobe lesions. Patients with right-sided cancers were more likely to have N2 disease compared with patients who had left-sided lesions (27% versus 21%, p = 0.02). CONCLUSIONS: There is a distinct predilection for the location of N2 disease based on the lobar location of primary nonsmall-cell lung cancer. We recommend the consideration of video-assisted thoracoscopy for biopsy of the 5 and 6 stations for patients with left upper lobe lesions, mediastinoscopy for right upper lobe lesions, and esophageal ultrasound with fine-needle aspiration for right lower lobe, left lower lobe, and right middle lobe lesions. Right-sided lesions are more likely to have N2 disease.

BACKGROUND: The accuracy of restaging in patients with stage IIIa non-small cell lung cancer after neoadjuvant chemoradiotherapy is unknown. METHODS: A prospective trial of patients with biopsy-proven N2 disease who underwent initial clinical staging with mediastinoscopy, integrated positron emission tomography/computed tomography (PET/CT), and CT. Patients then were clinically restaged by the same imaging techniques 4 to 12 weeks after their induction chemoradiation therapy and then underwent definitive pathologic staging. RESULTS: Ninety-three patients had their lymph nodes pathologically restaged. Repeat PET/CT after neoadjuvant therapy missed residual N2 disease in 13/65 (20%) patients and falsely suggested it in 7 of 28 (25%). It was more accurate than repeat CT for restaging at all pathologic stages (stage 0, 92% vs 39%, P = .03; and stage I 89% vs 36%, P = .04). When the maximum standardized uptake value of the primary tumor is decreased by 75% or more, it is highly likely (likelihood ratio, +LR, 6.1) the patient is a complete responder; when it decreased by 55% or more, it is highly likely (+LR, 9.1) the patient is a partial responder. When the maximum standardized uptake value of the N2 node initially involved with metastatic cancer is decreased by more than 50%, it is highly likely (+LR, 7.9) the node is now benign. CONCLUSION: Repeat integrated PET/CT is superior to repeat CT for the restaging of patients with stage IIIa non-small cell lung cancer. The percent decrease in the maximum standardized uptake value of the primary and of the involved lymph node is predictive of pathology; however, nodal biopsies are required since a persistently high maximum standardized uptake value does not equate to residual cancer.

In conclusion, chylothorax after esophagectomy is a devastating complication with high mortality rates if not corrected. A heightened awareness of this complication with early diagnosis and aggressive reoperation leads to excellent outcome. Reoperation is not indicated only when medical therapy significantly slows the daily loss of chyle and there are no metabolic consequences. The early decision to reoperate avoids the high morbidity of a persistently unchecked chylothorax. Reoperation should be based on the approach initially used for the esophagectomy, the location of the leak, and the side that has the chylothorax. The conduit should be handled carefully at the time of reoperation, the leak identified, the duct or the leaking nodal basin clipped and glued, and a pleurodesis performed. Following these principles minimizes the morbidity of a serious postoperative complication.

BACKGROUND: Thoracotomy is associated with significant pain and morbidity. METHODS: We performed a prospective randomized trial over 4 months. Patients were randomized to a standard posterior-lateral thoracotomy or an identical procedure, except an intercostal muscle was harvested from the lower rib (to protect the intercostal nerve) before chest retraction. To ensure an equal distribution among both groups, patients were stratified by race, sex, and type of pulmonary resection. All patients received similar pain management. Pain was assessed by using multiple pain scores during hospitalization and after discharge. Outcomes assessed were pain scores, spirometric values, analgesic use, and activity level. RESULTS: There were 114 patients. The median time for intercostal muscle harvesting was 3.7 minutes. The numeric pain scores were lower for the intercostal muscle group on postoperative days 1 and 2 and at weeks 1, 2, 3, 4, 8, and 12 (P < .05 for all). In addition, patients in the intercostal muscle group had a smaller decrease in spirometric values, were less likely to be using analgesics, and were more likely to have returned to normal activity. CONCLUSIONS: The harvesting of an intercostal muscle flap before chest retraction decreases the pain of thoracotomy and leads to a lower decrease in spirometry. In addition, patients have less pain at 1, 2, 3, 4, 8, and 12 weeks postoperatively and are less likely to be using narcotics. Finally, it offers a pedicled muscle flap that takes little time to harvest and is able to buttress all bronchi after lobectomy.

BACKGROUND: Mediastinoscopy and endoscopic ultrasound-guided fine-needle aspiration biopsy (EUS-FNA) are complementary for staging non-small cell lung cancer (NSCLC) patients. We assessed (1) the yield of EUS-FNA of malignant lymph nodes in NSCLC patients with combined anterior and posterior lymph nodes that had already undergone mediastinoscopy and (2) the cost implications associated with alternative initial strategies. METHODS: All patients underwent chest computed tomography (CT) and/or positron emission tomography (PET), and mediastinoscopy. Then, the posterior mediastinal stations (7, 8, and 9) or station 5 were targeted with EUS-FNA. The reference standard included thoracotomy with complete thoracic lymphadenectomy, repeat clinical imaging, or long-term clinical follow-up. A Monte Carlo cost-analysis model evaluated the expected costs and outcomes associated with staging of NSCLC. RESULTS: Thirty-five NSCLC patients met inclusion criteria (median age 65 years; 80% men). Endoscopic ultrasound-guided FNA was performed in 53 lymph nodes in various stations, the subcarinal station (7) being the most common (47.3%). Of the 35 patients who had a prior negative mediastinoscopy, 13 patients (37.1%) had malignant N2 or N3 lymph nodes. Accuracy of EUS-FNA (98.1%) was significantly higher than that of CT (41.5%; p < 0.001) and PET (40%; p < 0.001). Initial EUS-FNA resulted in average costs per patient of 1,867 dollars (SD +/- 4,308 dollars) while initial mediastinoscopy cost 12,900 dollars (SD +/- 4,164.40 dollars). If initial EUS-FNA is utilized rather than initial mediastinoscopy, an average cost saving of 11,033 dollars per patient would result. CONCLUSIONS: In patients with NSCLC and combined anterior and posterior lymph nodes, starting with EUS-FNA would preclude mediastinoscopy in more than one third of the patients. Endoscopic ultrasound-guided FNA is a safe outpatient procedure that is less invasive and less costly than mediastinoscopy.

BACKGROUND: The purpose of this study is to assess the safety and efficacy of pulmonary resection after low and high dose neoadjuvant radiotherapy with concurrent chemotherapy. PATIENTS AND METHODS: A retrospective cohort study using an electronic prospective database from January 1998 to August 2004. All patients had N2, stage IIIa, nonsmall cell lung cancer, and received neoadjuvant carboplatinum-based chemotherapy with similar doses. In addition, some patients received high-dose chest radiation (HD) equal to or greater than 60 Gy and were compared with those who received low-dose radiation (LD) less than 60 Gy. All bronchial stumps were buttressed with an intercostal muscle. RESULTS: There were 104 patients, 50 in the LD group and 54 patients in the HD group. Median dose of radiation was 45 Gy (range 35-50.4) in the LD group and 60 Gy (range 60-66.7) in the HD group. Complete pathologic response rate was 10% compared to 28% favoring the HD group (p = 0.04). Median length of stay for both groups was 4 days and the ICU was avoided in 74%. Major morbidity and mortality rates were similar: 8% compared to 9% and 2% compared to 3.7% for the low and high dose groups, respectively. Pneumonectomy was a significant risk factor for morbidity (OR = 17.0). CONCLUSIONS: Pulmonary resection after preoperative chest radiation is safe even after 60 Gy or higher. Sixty or higher may afford an increase in complete pathologic response and it does not seem to increase morbidity or mortality. However, if pneumonectomy is known to be required we prefer to avoid neoadjuvant radiotherapy and use chemotherapy alone.

BACKGROUND: Clinical stage affects the care of patients with nonsmall cell lung cancer. METHODS: This is a prospective trial on patients with suspected resectable nonsmall cell lung cancer. All patients underwent integrated positron emission tomographic scanning and computed tomographic scanning, and all suspicious metastatic sites were investigated. A, T, N, and M status was assigned. If N2, N3 and M1 were negative, patients underwent thoracotomy and complete thoracic lymphadenectomy. RESULTS: There were 383 patients. The accuracy of clinical staging using positron emission tomographic scanning and computed tomographic scanning was 68% and 66% for stage I, 84% and 82% for stage II, 74% and 69% for stage III, and 93% and 92% for stage IV, respectively. N2 disease was discovered in 115 patients (30%) and was most common in the subcarinal lymph node (30%). Unsuspected N2 disease occurred in 28 patients (14%) and was most common in the posterior mediastinal lymph nodes (subcarinal, 38%; posterior aortopulmonary, 15%). It was found in 9% of patients who were clinically staged I (58% in the posterior mediastinal lymph nodes) and in 26% of patients clinically staged II (86% in posterior mediastinal lymph nodes). CONCLUSIONS: Despite integrated positron emission tomographic scanning and computed tomographic scanning, clinical staging remains relatively inaccurate for patients with nonsmall cell lung cancer. Recent studies suggest adjuvant therapy for stage Ib and II nonsmall cell lung cancer; thus the impact on preoperative care is to find unsuspected N2 disease. Unsuspected N2 disease is most common in posterior mediastinal lymph nodes inaccessible by mediastinoscopy. Thus one should consider endoscopic ultrasound fine-needle aspiration, especially for patients clinically staged as I and II, even if the nodes are negative on positron emission tomographic scanning and computed tomographic scanning.