Mediastinal Staging in Non-Small Cell Lung Cancer.

In the absence of distant metastases, lung cancer treatment is determined by the results of mediastinal lymph node staging. Occult mediastinal lymph node metastases can be missed by radiologic and needle-based staging methods. Aggressive staging of mediastinal lymph nodes improves staging accuracy. Improved accuracy of mediastinal lymph node staging results in more appropriate lung cancer treatment. Improved accuracy of mediastinal lymph node staging can improve stage-specific survival from lung cancer.

Surgical staging for non-small cell lung cancer.

The treatment of non-small cell lung cancer is stage specific. Aggressive staging is associated with improved stage-specific prognosis. Available methods of surgical staging include scalene node biopsy, mediastinoscopy, anterior mediastinotomy, and thoracoscopy. In this article the various surgical staging methods are described and their respective roles are discussed.

Pneumonectomy for lung cancer after preoperative concurrent chemotherapy and high-dose radiation.

BACKGROUND: We studied the clinical characteristics and outcomes of patients undergoing pneumonectomy after preoperative concurrent chemoradiation for non-small cell lung cancer. METHODS: Clinical records of patients with non-small cell lung cancer who underwent pneumonectomy at our institution between 1995 and 2005 after preoperative concurrent chemoradiation were reviewed retrospectively. RESULTS: Twenty-nine patients underwent pneumonectomy after preoperative concurrent chemoradiation. Of the 21 men and 8 women who were treated, 1 had stage IIB (T3N0M0) and the remainder had stage IIIA or IIIB non-small cell lung cancer. Mean patient age at surgery was 53.4 years. There were 15 right pneumonectomies, of which 2 were for pancoast tumors. All patients received concurrent preoperative chemoradiation. Mean total radiation dose was 61.1 Gy. All patients went on to have complete (R0) resection by pneumonectomy. Pathologic complete response was found in 16 patients (55.2%). All patients were discharged alive from the hospital after pneumonectomy. Median hospital length of stay was 5 days (mean 8.6). Ninety-day mortality after surgery was 3.4% (n = 1). Recurrences have been found in 11 patients (38%), including brain metastases (n = 6), bone metastases (n = 4), liver metastases (n = 2), and cervical lymph node metastases (n = 2). One patient had a contralateral new primary lung cancer develop 70 months after undergoing pneumonectomy. Estimated 5-year disease-free survival is 48%. Median survival time has not been reached. CONCLUSIONS: Pneumonectomy can be performed safely after preoperative concurrent chemoradiation, even with high-dose radiation. The frequency of disease recurrence in the brain underscores the need to evaluate the role of prophylactic cranial radiation in non-small cell lung cancer.

Combined transcervical and unilateral-thoracoscopic thymectomy for myasthenia gravis: 2 years of follow-up.

BACKGROUND: To investigate the efficacy of combined transcervical and unilateral-thoracoscopic thymectomy for myasthenia gravis. METHODS: There were 36 patients with nonthymomatous myasthenia gravis, undergoing combined transcervical and unilateral-thoracoscopic thymectomy and who have been followed-up for more than 2 years. To achieve maximal benefit, a transverse cervical incision was performed to give access to remove fat in the neck, which may contain residual or ectopic thymus after all thymic tissue and mediastinal fat were completely removed by thoracoscopic thymectomy. RESULTS: There were no perioperative deaths and no cases that required conversion to median sternotomy. The mean length of surgery was 162 minutes (range, 132 to 210 min). Three sustained myasthenic crisis. Seventeen patients had lymphadenitis and 4 had ectopic thymus in the neck. There were 2 cases in which the residual superior horns of thymus were found in the neck. Average specimen weights of the thymus, mediastinal fat, and cervical fat were 44.2, 32.5, and 3.6 g, respectively. The rate of complete stable remission was 16.7% at the end of the first year, and rose to 27.8% at the second year. The effective rate was 88.9% at the end of the second year. CONCLUSIONS: Thymectomy represents a safe and valid approach for patients with myasthenia gravis. Achieving a curative thymectomy and good cosmesis in myasthenic patients is possible with the combined transcervical and unilateral-thoracoscopic thymectomy as an effective alternative to open approaches.

Phase I/II trial of hyperfractionated radiation and chemotherapy followed by surgery in stage III lung cancer.

BACKGROUND: We have previously demonstrated that high-dose chemoradiotherapy followed by resection for patients selected on the basis of mediastinal sterilization was feasible and resulted in excellent outcomes. This study was designed to determine the ability to intensify our prior approach utilizing hyperfractionated radiation and more aggressive consolidative chemotherapy. METHODS: Patients with documented stage IIIA/B nonsmall-cell lung cancer, performance status 0 to 2, and adequate organ function were eligible. A phase I portion utilized escalating doses of carboplatin and vinorelbine, commencing with areas under the curve of 1 and 5 mg/m(2), respectively, and concurrent 69.6 Gy hyperfractionated radiotherapy. A phase II portion utilized the identical radiotherapy with carboplatin/vinorelbine at the maximum tolerated dose established in phase I. Patients for whom mediastinal nodal clearance was demonstrated underwent resection. All patients were to receive consolidation chemotherapy consisting of carboplatin/vinorelbine for three cycles, followed by docetaxel for three cycles. Prophylactic cranial irradiation was offered to patients after completion of therapy. RESULTS: Forty-seven patients participated in the study (33 IIIA, 14 IIIB; 15 men, 32 women; median age, 56 years). The maximum tolerated dose for concurrent carboplatin/vinorelbine and hyperfractionated radiotherapy was established at areas under the curve of 1 and 10 mg/m(2), respectively. Twenty-eight patients completed trimodality treatment including surgery. Median survival time for the entire study cohort (n = 47) is 29.6 months, and it is 55.8 months for patients with mediastinal clearance who underwent resection (n = 28). CONCLUSIONS: Surgical resection of locally advanced stage IIIA and IIIB nonsmall-cell lung cancer after induction hyperfractionated radiation and concurrent chemotherapy is safe and well tolerated. Whether this approach is superior to less aggressive therapy is uncertain and will require comparative studies.

Stratified analysis of clinical outcomes in thoracoscopic sympathicotomy for hyperhidrosis.

BACKGROUND: The primary goal of this study is to identify clinical variables associated with successful surgical treatment for hyperhidrosis and facial blushing. METHODS: Six hundred eight thoracoscopic sympathicotomies were performed in 304 patients. Retrospective stratified analysis of patients after thoracoscopic sympathicotomy for hyperhidrosis or facial blushing and having completed follow-up of at least 6 months (n = 232) was performed. Preoperative and postoperative quality-of-life indices (range, 0 to 3) were used to measure impact of surgery, and comparisons were indexed to preoperative symptoms. Postoperative compensatory sweating was analyzed with respect to the level(s) of sympathetic chain division. RESULTS: Thoracoscopic sympathicotomy was performed at level T2 alone in 5% of patients; levels T2 to T3 in 63% of patients; levels T3 to T4 in 3% of patients; levels T2 to T4 in 14% of patients; and more than three levels in 14% of patients. In hyperhidrosis patients, mean preoperative quality-of-life index was 2.0 and postoperative quality-of-life index was 0.4 (p < 0.001). Facial blushers had preoperative and postoperative quality-of-life index of 2.6 and 1.0, respectively. Significant compensatory sweating was seen in 33% patients overall and occurred in 29% of patients with palmar symptoms, 26% of axillary patients, and 42% of facial blushers. Significant compensatory sweating in relation to the level(s) of sympathetic chain division occurred in T2 alone, 45%; T2 to T3, 30%; T3 to T4, 14%; T2 to T4, 38%; and more than three levels, 49%. CONCLUSIONS: Significant improvement in quality of life can result from surgery for hyperhidrosis. However, the incidence of postoperative compensatory sweating may be dependent on the level of sympathicotomy performed. The choice of sympathicotomy level(s) should be directed toward reducing the incidence of significant compensatory sweating while simultaneously ensuring relief of primary preoperative symptoms.

Different characteristics of nonthymomatous generalized myasthenia gravis with and without oropharyngeal involvement.

BACKGROUND: Thymectomy represents a safe and valid approach for patients with myasthenia gravis. However, some factors may influence the efficacy of thymectomy. The objective of this study was to evaluate the clinical characteristics of generalized myasthenia gravis with oropharyngeal involvement and compare the postoperative outcome of generalized myasthenia gravis without and with oropharyngeal involvement. METHODS: From 1991 to 2002, there were 202 patients with nonthymomatous generalized myasthenia gravis (GMG), who underwent thymectomy by the transsternal approach or thoracoscopy. According to the clinical classification of the Myasthenia Gravis Foundation of America (MGFA), these patients have been subdivided into two groups: GMG without oropharyngeal involvement and GMG with oropharyngeal involvement. Complete stable remission, as defined by the MGFA Medical Task Force, was the primary endpoint for efficacy. RESULTS: In all, 182 patients were followed up for at least 5 years. There were 135 cases of GMG without oropharyngeal involvement and 47 cases of GMG with oropharyngeal involvement. There were significant differences in postoperative pneumonia, ventilatory support time, and myasthenic crisis between patients with GMG with and without oropharyngeal involvement (p values were 0.040, 0.021, and 0.007, respectively). At 5 years of follow-up, the cumulative probability of reaching complete stable remission in GMG without oropharyngeal involvement was 18.5% at the end of the first year, and rose steadily in subsequent years (26.7%, 37.0%, 39.1%, and 40% at 2, 3, 4, and 5 years, respectively). In GMG with oropharyngeal involvement, it was 6.4%, 14.9%, 23.4%, 29.9%, and 31.9%, respectively, in the continual follow-up years. The first 3 years were associated with a significantly greater probability of achieving complete stable remission (p = 0.047 for the first year, p = 0.025 for the second one, and p = 0.048 for the third one). The later 2 years had no significant difference on complete stable remission. CONCLUSIONS: Laryngeal myasthenia gravis is more severe and the prognosis after thymectomy is not as optimistic as for patients without oropharyngeal involvement.

Clinical experience in 397 consecutive thoracoscopic sympathectomies.

BACKGROUND: The purpose of this study is to evaluate the safety and efficacy of thoracoscopic sympathectomy for the treatment of hyperhidrosis, blushing, reflex sympathetic dystrophy, and digital ischemia. METHODS: We conducted a retrospective review of 202 patients who underwent thoracoscopic sympathectomy at the University of Maryland from March 1992 to April 2003. RESULTS: Three hundred ninety-seven procedures were performed on 202 patients (105 women, 97 men). Mean age was 29 years (range, 9 to 65). Indications for surgery included hyperhidrosis, facial blushing, digital ischemia, and reflex sympathetic dystrophy. Synchronous bilateral sympathectomies were performed in 194 patients; right side alone (n = 6); left side alone (n = 1); 1 patient had staged bilateral sympathectomies. Single incision with lung isolation technique was used. There was no mortality. Preoperative symptoms resolved completely or significantly improved in greater than 90% of patients. One patient with reflex sympathetic dystrophy recurred and 1 patient with hyperhidrosis complained of significant compensatory sweating. Compensatory sweating to a lesser degree occurred in approximately one third of patients. Complications included asymptomatic pleural effusion (n = 1), pneumothorax (n = 1), and reoperation for chylothorax that was identified early (n = 1). In 2 patients treated for facial blushing, Horner's syndrome developed postoperatively; 1 of them subsequently underwent blepharoplasty. In 3 patients, hyperesthesias developed at the incision. CONCLUSIONS: Thoracoscopic sympathectomy can be performed safely and with excellent results. Compensatory sweating is the main side effect, although significant complaints from this are rare. Horner's syndrome remains an extremely uncommon complication as a result of thoracoscopic sympathectomy at our institution.

Multimodality treatment of esophageal cancer.

Stage specific management of non-small cell lung cancer is widely accepted. The use of pretreatment disease stage to guide therapy for esophageal cancer is an intellectually appealing concept. To date, there isa relative lack of data upon which one may base stage specific treatment decisions for esophageal carcinoma. This is because thorough pretreatment TNM staging is not universally practiced. As a result, stage-specific treatment varies widely. Based upon the available data, surgery alone may be appropriate for resectable, node-negative disease. In the case of clearly un-resectable disease, definitive chemoradiation is indicated.The value of neoadjuvant or adjuvant treatment modalities in the case of clearly resectable node-negative disease (TlN0 or T2N0) is questionable;however, in the presence of lymph node involvement (N1), or in the case of a marginally resectable primary tumor (T3 or T4), neoadjuvant chemoradiation is probably indicated. Although the achievement ofa complete pathologic response following chemoradiation may obviate surgical resection, even microscopic residual cancer can result in local recurrence. To date, there is no reliable method of ascertaining a complete pathologic response before surgical resection. Therefore, when feasible, the addition of surgical resection following chemoradiation is warranted. Future treatment trials for esophageal cancer should include rigorous pretreatment staging protocols to elucidate stage-specific results of therapy.

High-dose radiotherapy in trimodality treatment of Pancoast tumors results in high pathologic complete response rates and excellent long-term survival.

OBJECTIVE: We sought to study the clinical characteristics and outcomes of patients treated with a surgery-inclusive multimodality approach for Pancoast tumors. METHODS: Clinical records of patients with Pancoast lung cancer who were enrolled for multimodality treatment between 1993 and 2003 at our institution were reviewed retrospectively. RESULTS: Thirty-six patients completed neodjuvant chemoradiation followed by en bloc surgical resection, whereas one patient received high-dose radiation alone followed by surgical intervention. There were 22 men and 15 women. Thirty-four lobectomies and 3 pneumonectomies were performed. Pretreatment non-small cell lung cancer stages were IIB, IIIA, IIIB, and IV (presenting with solitary brain metastasis) in 18, 8, 6, and 5 cases, respectively. R0 resection was achieved in 36 (97.3%) patients. Operative mortality was 2.7% (n = 1). High-dose radiotherapy was successfully tolerated in all but 1 patient. Mean total radiation dose was 56.9 Gy. Pathologic complete response was found in 40.5% (n = 15) of patients. Recurrences were found in 50% (n = 18) of patients. Brain metastasis was the most common recurrence (n = 9), followed by other distant recurrences (n = 4) and local recurrences (n = 5). Median survival time for the group is 2.6 years, and median survival time (pathologic complete response) is 7.8 years. It is noteworthy that median survival time of patients with positive pretreatment lymph nodes (12 patients) was not reached. CONCLUSIONS: Surgical resection of Pancoast tumors after neoadjuvant high-dose radiation and chemotherapy can be safely performed. High-dose radiation in trimodality treatment is well tolerated and might be beneficial. Similar to other studies, late central nervous system relapse is problematic and indicates a need for assessing the role of prophylactic cranial irradiation in this disease.

Pulmonary resection after curative intent radiotherapy (>59 Gy) and concurrent chemotherapy in non-small-cell lung cancer.

BACKGROUND: Pulmonary resection after chemotherapy and concurrent full-dose radiotherapy (>59 Gy) has previously been associated with unacceptably high morbidity and mortality. Subsequently neoadjuvant therapy protocols have used reduced and potentially suboptimal radiotherapy doses of 45 Gy. We report a series of 40 patients with locally advanced non-small-cell lung cancer who successfully underwent pulmonary resection after receiving greater than 59 Gy radiation and concurrent chemotherapy. Operative results and midterm survival follow-up are presented. METHODS: Data were reviewed from 40 consecutive patients who underwent lung resection after receiving high-dose radiotherapy and concurrent platinum-based chemotherapy between January 1994 and May 2000. The follow-up closing interval for this study was until August 2003 or time of death. RESULTS: Preoperative stage was IIb (7 patients), IIIA (21 patients), IIIB (10 patients), and IV (2 patients with isolated brain metastasis). Thirteen patients exhibited Pancoast tumors. Median time from completion of induction therapy to surgery was 53 days. Twenty-nine lobectomies and 11 pneumonectomies (7 right, 4 left) were performed. There were no postoperative deaths. Intercostal muscle flaps were used prophylactically in all but one pneumonectomy patient. Seven patients required perioperative transfusions. Median intensive care unit (ICU) time averaged 2 days and the total length of stay was 6 days. One patient exhibited postpneumonectomy pulmonary edema and a bronchopleural fistula developed in another patient (not receiving an intercostal muscle flap). Thirty-four of 40 patients (85%; 95% CI: 70%-94%) were downstaged pathologically, 33 out of 40 patients (82.5%, 95% confidence interval [CI]: 67%-93%) indicated no residual lymphadenopathy, and 18 out of 40 patients (45%, 95% CI: 29%-61%) exhibited a complete pathologic response. Median follow-up was 2.8 years. The 1-, 2-, and 5-year overall survival rates were 92.4%, 66.7%, and 46.2%, respectively. Disease-free 1-, 2-, and 5-year survival rates were 73.0%, 67.2%, and 56.4%, respectively. Median disease-free survival has not been reached. CONCLUSIONS: Pulmonary resection may be performed safely after curative intent concurrent chemotherapy and radiotherapy to greater than 59 Gy. High pathologic complete response rates and sterilization of mediastinal lymph nodes were observed accompanied by highly favorable survival rates. This experience, though promising, will require confirmation in a prospective multiinstitutional clinical trial.

Operative techniques for lung volume reduction surgery.

Recently, LVRS has received renewed public interest. Various surgical approaches and techniques exist, and each has challenges, advantages, and disadvantages. Stapled techniques have been used more commonly than plication techniques or lasers. The choice of staple buttressing material has not been shown to affect outcome. For most patients who are suitable for LVRS, a bilateral procedure is appropriate. Minimally invasive techniques are gaining in popularity and have demonstrated good results. Of the approaches discussed above, bilateral thoracoscopy in the supine position is likely to be the most expeditious with the lowest incision-related morbidity and dysfunction.

Immunohistochemistry analysis of micrometastasis in pretreatment lymph nodes from patients with esophageal cancer.

BACKGROUND: With recent advances in neoadjuvant therapy in esophageal cancer, pretreatment lymph node staging has become increasingly important in stratifying patients to appropriate treatment regimens and for prognostication. Immunohistochemical analysis (IHC) using epithelial markers has been shown to identify micrometastases in histologically negative lymph nodes. We performed this study to evaluate if IHC analysis in thoracoscopic/laparoscopic (Ts/Ls) pretreatment staging lymph nodes can reveal additional diagnostic information to routine histopathology. METHODS: Specimens of 106 patients with esophageal cancer who had pretreatment Ts/Ls staging were retrospectively studied. Lymph node biopsies were obtained for IHC staining using cytokeratin (CK) of AE1/AE3. IHC staining for p53, an apoptosis protein associated with poor prognosis in esophageal cancer, was also performed. RESULTS: 331 Ts/Ls staging lymph node biopsies were collected from 106 patients. A total of 15.4% (51/331) of the lymph nodes or 34.9% (37/106) of patients were found to have metastatic deposits by routine histology. All the histologically positive lymph nodes were CK positive. Among the remaining 280 histologically negative lymph nodes, 11(3.9%) were found to have micrometastasis by CK staining. Three patients (4.3%, 3/69) were upstaged from N0 to N1. They died of early recurrences after treatment. A total of 67.6% (25/37) of the patients with histologically positive lymph node were p53 positive. No histologically negative lymph node was found to be p53 positive in this series. CONCLUSIONS: Immunohistochemical analysis for CK can detect micrometastatic involvement of lymph nodes that are missed on routine pathologic examination, and, therefore, can improve lymph node staging. Its clinical significance in esophageal cancer warrants further study.

Thoracoscopy/laparoscopy in the staging of esophageal cancer: Maryland experience.

Precise clinical staging of esophageal cancer before treatment is important. Thoracoscopic/laparoscopic (Ts/Ls) staging has been proposed as a promising staging method. This study was conducted to evaluate the potential benefits of Ts/Ls staging over conventional noninvasive clinical staging in patients with esophageal cancer. From 1991 to 1999, 111 patients with esophageal cancer underwent Ts/Ls staging by the University of Maryland Medical System. Pretreatment staging workup included computed tomography, magnetic resonance imaging, and esophageal ultrasonography, followed by Ts/Ls surgical staging. Thoracoscopy was successfully performed in 102 patients and was aborted in 4 patients because of pleural adhesions. Laparoscopy was successfully done in 76 patients and was aborted in 1 patient because of peritoneal adhesion. Sixty-seven patients had both Ts and Ls staging, whereas 35 patients and 9 patients, respectively, had only Ts or Ls staging. Thirteen of 19 patients with clinical T4 disease were downstaged to T3 disease, and 8 patients with clinical T3 disease were upstaged to T4 by Ts/Ls staging. No clinical T1-2 disease was found to be associated with local invasion (T4) by Ts/Ls. Forty-eight and 19 patients had mediastinal and celiac lymph node metastases clinically diagnosed, respectively. Nine (18.8%) and 12 (63.2%) of them were proved by Ts and Ls, respectively. An additional 5 and 16 patients were found to have unexpected mediastinal and celiac lymph node metastases, respectively, by Ts/Ls. Biopsy specimens of pleura, lung, or liver were obtained by Ts/Ls procedures in 17 patients because of suspicious findings of routine imaging studies or unexpected findings during the staging operation. Five patients were found to have distant metastasis, and the presence of metastases in others was excluded. The correlation between Ts/Ls staging and conventional noninvasive clinical staging in the diagnosis of T4 disease, mediastinal lymph node metastasis, celiac lymph node metastasis, and M1 disease was 18.8%, 14.5%, 25.5%, and 20.0%, respectively. Ts/Ls provides more accurate information for evaluating local invasion, lymph node metastasis, and distant metastasis. The poor correlation of staging diagnosis between Ts/Ls and conventional noninvasive clinical examinations suggests that the accuracy of current noninvasive clinical staging is questionable and needs to be improved.

Thoracoscopic and laparoscopic lymph node staging in esophageal cancer: do clinicopathological factors affect the outcome?

BACKGROUND: This study was performed to evaluate the pattern of lymphatic metastases found by combined thoracoscopic (TS) and laparoscopic (LS) lymph node staging in esophageal cancer, and ascertain whether clinicopathologic factors may be used to guide the clinical practice of combined TS and LS staging. METHODS: A retrospective study was performed in a series of 76 esophageal cancer patients who had undergone both TS and LS staging before treatment. The correlation of TS and LS lymph node metastases with clinicopathologic factors was analyzed, including the clinical T stage, clinical N stage, tumor location, and histology. RESULTS: Thirty-one patients (40.8%) were found to have lymphatic metastasis by TS and LS staging. Among them, 22 patients had abdominal lymph node metastases, 7 patients had mediastinal lymph node metastases, and 2 patients had both. Patients with advanced T stage (T3 to T4) or adenocarcinoma had a higher frequency of abdominal lymphatic metastases than patients with early T stage (T1 to T2) (39% vs 16%; p = 0.04) or squamous cell carcinoma (39% vs 20%; p = 0.079), respectively. Patients with clinical abdominal N1 stage had a higher incidence of positive laparoscopic finding than patients with clinical abdominal N0 stage (67% vs 23%; p = 0.001). There was no significant correlation between lymphatic metastases and the location of the primary tumor. CONCLUSIONS: Clinicopathologic factors, including the histologic type, the clinical T stage, and abdominal N stage, may affect the outcome of TS and LS lymph node staging in esophageal cancer patients. This clinicopathologic impact may play a role for the selection of candidates for TS and LS staging, and also allows surgeons to focus their attention on the most likely high-yield biopsy targets.