Richard Inculet

Randomized trial of mediastinal lymph node sampling versus complete lymphadenectomy during pulmonary resection in the patient with N0 or N1 (less than hilar) non-small cell carcinoma: Results of the American College of Surgery Oncology Group Z0030 Trial

OBJECTIVE To determine whether mediastinal lymph node dissection improves survival compared with mediastinal lymph node sampling in patients undergoing resection for N0 or nonhilar N1, T1, or T2 non-small cell lung cancer. METHODS Patients with non-small cell lung cancer underwent sampling of 2R, 4R, 7, and 10R for right-sided tumors and 5, 6, 7, and 10L for left-sided tumors. If all tumors were negative for malignancy, patients were randomized to no further lymph node sampling (mediastinal lymph node sampling) or complete mediastinal lymph node dissection. RESULTS Of 1111 patients randomized, 1023 (mediastinal lymph node sampling in 498, mediastinal lymph node dissection in 525) were eligible and evaluable. There were no significant differences between the 2 groups in terms of demographics, Eastern Cooperative Oncology Group status, histology, cancer location, type or extent of resection, and pathologic stage. Occult N2 disease was found in 21 patients in the mediastinal lymph node dissection group. At a median follow-up of 6.5 years, 435 patients (43%) have died: mediastinal lymph node sampling in 217 (44%) and mediastinal lymph node dissection in 218 (42%). The median survival is 8.1 years for mediastinal lymph node sampling and 8.5 years for mediastinal lymph node dissection (P = .25). The 5-year disease-free survival was 69% (95% confidence interval, 64-74) in the mediastinal lymph node sampling group and 68% (95% confidence interval, 64-73) years in the mediastinal lymph node dissection group (P = .92). There was no difference in local (P = .52), regional (P = .10), or distant (P = .76) recurrence between the 2 groups. CONCLUSIONS If systematic and thorough presection sampling of the mediastinal and hilar lymph nodes is negative, mediastinal lymph node dissection does not improve survival in patients with early stage non-small cell lung cancer, but these results are not generalizable to patients staged radiographically or those with higher stage tumors.

Video-assisted thoracic surgery versus open lobectomy for lung cancer: a secondary analysis of data from the American College of Surgeons Oncology Group Z0030 randomized clinical trial.

OBJECTIVE Video-assisted thoracoscopic lobectomy remains controversial. We compared outcomes from participants in a randomized study comparing lymph node sampling versus dissection for early-stage lung cancer who underwent either video-assisted thoracoscopic or open lobectomy. METHODS Data from 964 participants in the American College of Surgeons Oncology Group Z0030 trial were used to construct propensity scores for video-assisted thoracoscopic versus open lobectomy (based on age, gender, histology, performance status, tumor location, and T1 vs T2). Propensity scores were used to estimate the adjusted risks of short-term outcomes of surgery. Patients were classified into 5 equal-sized groups and compared using conditional logistic regression or repeated measures analysis of variance. RESULTS A total of 752 patients (66 video-assisted and 686 open procedures) were analyzed on the basis of propensity score stratification. Median operative time was shorter for video-assisted thoracoscopic lobectomy (video-assisted thoracoscopy 117.5 minutes vs open 171.5 minutes; P < .001). Median total number of lymph nodes retrieved (dissection group only) was similar (video-assisted thoracoscopy 15 nodes vs open 19 nodes; P = .147), as were instances of R1/R2 resection (video-assisted thoracoscopy 0% vs open 2.3%; P = .368). Patients undergoing video-assisted thoracoscopic lobectomy had less atelectasis requiring bronchoscopy (0% vs 6.3%, P = .035), fewer chest tubes draining greater than 7 days (1.5% vs 10.8%; P = .029), and shorter median length of stay (5 days vs 7 days; P < .001). Operative mortality was similar (video-assisted thoracoscopy 0% vs open 1.6%, P = 1.0). CONCLUSION Patients undergoing video-assisted lobectomy had fewer respiratory complications and shorter length of stay. These data suggest video-assisted thoracoscopic lobectomy is safe in patients with resectable lung cancer. Longer follow-up is needed to determine the oncologic equivalency of video-assisted versus open lobectomy.

Factors affecting cervical anastomotic leak and stricture formation following esophagogastrectomy and gastric tube interposition

Following esophagectomy, restoration of swallowing by gastric tube interposition with cervical esophagogastric anastomosis reduces morbidity and mortality associated with intrathoracic anastomoses at the expense of an increased incidence of both anastomotic leak and stricture formation. A retrospective study of 165 patients with either squamous cell carcinoma or adenocarcinoma of the distal esophagus or gastric cardia undergoing esophagogastrectomy with gastric tube interposition and cervical anastomosis at Vancouver, British Columbia, or London, Ontario, was undertaken. Forced-entry multiple logistic regression analysis of factors believed to influence anastomotic outcome was performed. Anastomotic leak occurred in 17% of patients; statistically significant correlation with low preoperative serum albumin (p = 0.005), running suture technique (p = 0.029), high intraoperative blood loss (p = 0.038), and the occurrence of postoperative delayed gastric emptying (p = 0.045) was found. Anastomotic strictures occurred in 31% of patients; a statistically significant correlation was found with preceding anastomotic leak (p = 0.001) and intraoperative blood loss (p = 0.042). Factors including preoperative radiotherapy and diabetes mellitus were not found to be significant.

Propranolol for the prevention of postoperative arrhythmias in general thoracic surgery

BACKGROUND Prevention of postoperative arrhythmias in patients undergoing general thoracic surgery is desirable to prevent morbidity. METHODS A randomized, double-blind, placebo controlled trial of propranolol (10 mg every 6 hours) for 5 days was undertaken in patients undergoing major thoracic operations to determine whether arrhythmias requiring treatment could be reduced. Secondary outcomes included overall arrhythmia rate, adverse events, and length of stay. Arrhythmias were assessed by 72-hour Holter monitoring. Patients with a history of heart failure, asthma, advanced heart block, preexisting arrhythmias, sensitivity to propranolol, or use of antiarrhythmic drugs were excluded. RESULTS Using the intention-to-treat principle there was a 70% relative risk reduction from 20% to 6% in the rate of treated arrhythmias with propranolol (p = 0.071, 95% confidence interval 0.6% to 27.2%). Overall arrhythmias were common but usually benign. Adverse effects were common, although generally mild with hypotension and bradycardia being reported more often in the propranolol group. Length of stay was not different. CONCLUSIONS There was a trend to a reduction in the risk of perioperative arrhythmias with propranolol. Moreover, propranolol was well tolerated showing a slight increase in minor adverse events.

Thoracoscopic versus laparoscopic modified Heller Myotomy for achalasia: efficacy and safety in 87 patients.

BACKGROUND The ideal treatment for achalasia permanently eliminates the dysfunctional lower esophageal sphincter, relieving dysphagia and regurgitation; prevents gastroesophageal reflux; and has an acceptable morbidity rate. Controversy exists concerning whether the thoracoscopic Heller Myotomy (THM) or laparoscopic Heller myotomy (LHM) technique is the best approach to a modified Heller myotomy for achalasia. STUDY DESIGN We performed a retrospective comparison of the patient characteristics, operative results, postoperative symptoms, and the learning curves for the procedures of 24 patients undergoing THM and 63 patients undergoing LHM between 1991 and 1998. RESULTS Preoperative patient variables in each group revealed similar distributions for age, gender, and prevalence of previous pneumatic dilation. Mean operating room (OR) times were 4.3 hours (range 2.9 to 5.6 hours) for THM and 3.0 hours (range 1.5 to 6.5 hours) for LHM (p = 0.01). Three esophageal perforations occurred in the THM group and two in the LHM group. Conversion to an open procedure took place in five THM operations (21%) and one LHM operation (2%) (p = 0.005). There were no postoperative esophageal leaks. Mean postoperative length of stay (LOS) for THM was 6.1 days (range 1 to 17 days) and for LHM was 4.0 days (range 1 to 12 days) (p = 0.03). Learning-curve analysis of the first 24 LHM patients compared with the most recent 24 revealed greater OR time in the first 24 mean 3.6 hours, (range 2.0 to 6.5 hours) versus mean 2.3 hours, (range 1.5 to 3.7 hours; p = 0.01), and greater LOS mean 5.5 days, (range 3 to 12 days) versus mean 3.1 days, (range 1 to 8 days; p < 0.01). One esophageal perforation occurred in each subgroup. A similar analysis in the first 12 THM patients compared with the most recent 12 revealed no significant improvement in OR times or LOS. Three esophageal perforations occurred in the latter subgroup only. All patients had preoperative daily dysphagia to solids. Followup data for LHM (n = 49) (median 17 months, range 1 to 39 months) and THM (n = 15) (median 42 months, range 1 to 69 months) revealed no or minimal dysphagia in 90% (44 of 49) after LHM and 31% (4 of 13) after THM (p < 0.01). No or minimal heartburn was present in 89% (41 of 46) after LHM and 67% (8 of 12) after THM (p < 0.05). Regurgitation was absent or minimal in 94% (46 of 49) after LHM and 86% (12 of 14) after THM (p = 0.3). CONCLUSIONS LHM was associated with decreased OR time, decreased rate of conversion to an open procedure, and shorter LOS compared with THM. LHM was superior to THM in relieving dysphagia and preventing heartburn. LHM may be the preferred surgical treatment of achalasia in some patients.

Positron Emission Tomography-Computed Tomography Compared with Invasive Mediastinal Staging in Non-small Cell Lung Cancer: Results of Mediastinal Staging in the Early Lung Positron Emission Tomography Trial

Introduction: Patients with non-small cell lung cancer (NSCLC) require careful preoperative staging to define resectability for potential cure. 18Fluorodeoxyglucose positron emission tomography combined with computed tomography (18FDG PET-CT) is widely used to stage NSCLC. If the mediastinum is positive on PET-CT examination, some practitioners conclude that the patient is inoperable and refer the patient for nonsurgical treatment. Methods: In this analysis of a previously reported trial comparing PET-CT with conventional imaging in the diagnostic work-up of patients with clinical stage I, II, or IIIA NSCLC, we determined the accuracy of PET-CT in mediastinal staging compared with invasive mediastinal staging either by mediastinoscopy alone or by mediastinoscopy combined with thoracotomy. Results: All 149 patients had mediastinal nodal staging at mediastinoscopy alone (14), thoracotomy alone (64), or both (71). The sensitivity of PET-CT was 70% (95% confidence interval [CI], 48–85%), and specificity was 94% (95% CI, 88–97%). Of 22 patients with a PET-CT interpreted as positive for mediastinal nodes, 8 did not have tumor. The positive predictive value and negative predictive value were 64% (95% CI, 43–80%) and 95% (95% CI, 90–98%), respectively. Based on PET-CT alone, eight patients would have been denied potentially curative surgery if the mediastinal abnormalities detected by PET-CT had not been evaluated with an invasive mediastinal procedure. Conclusions: PET-CT assessment of the mediastinum is associated with a clinically relevant false-positive result. Our study confirms the need for pathologic confirmation of mediastinal lymph node abnormalities detected by PET-CT.

Number of Lymph Nodes Harvested From a Mediastinal Lymphadenectomy: Results of the Randomized, Prospective American College of Surgeons Oncology Group Z0030 Trial

BACKGROUND Lymph node status is a major determinant of stage and survival in patients with lung cancer; however, little information is available about the expected yield of a mediastinal lymphadenectomy. METHODS The American College of Surgeons Oncology Group Z0030 prospective, randomized trial of mediastinal lymph node sampling vs complete mediastinal lymphadenectomy during pulmonary resection enrolled 1,111 patients from July 1999 to February 2004. Data from 524 patients who underwent complete mediastinal lymph node dissection were analyzed to determine the number of lymph nodes obtained. RESULTS The median number of additional lymph nodes harvested from a mediastinal lymphadenectomy following systematic sampling was 18 with a range of one to 72 for right-sided tumors, and 18 with a range of four to 69 for left-sided tumors. The median number of N2 nodes harvested was 11 on the right and 12 on the left. A median of at least six nodes was harvested from at least three stations in 99% of patients, and 90% of patients had at least 10 nodes harvested from three stations. Overall, 21 patients (4%) were found to have occult N2 disease. CONCLUSIONS Although high variability exists in the actual number of lymph nodes obtained from various nodal stations, complete mediastinal lymphadenectomy removes one or more lymph nodes from all mediastinal stations. Adequate mediastinal lymphadenectomy should include stations 2R, 4R, 7, 8, and 9 for right-sided cancers and stations 4L, 5, 6, 7, 8, and 9 for left-sided cancers. Six or more nodes were resected in 99% of patients in this study. TRIAL REGISTRY ClinicalTrials.gov; No.: NCT00003831; URL: clinicaltrials.gov.

Current Concepts in the Management of Esophageal Perforations: A Twenty-Seven Year Canadian Experience

BACKGROUND Perforation of the esophagus remains a challenging clinical problem. METHODS A retrospective review was performed of patients diagnosed with an esophageal perforation admitted to the London Health Sciences Centre from 1981 to 2007. Univariate and multivariate logistic regression was used to determine which factors had a statistically significant effect on mortality. RESULTS There were 119 patients; 15 with cervical, 95 with thoracic, and 9 with abdominal perforations. Fifty-one percent of all the perforations were iatrogenic and 33% were spontaneous. Multivariate logistic regression analysis revealed that patients with preoperative respiratory failure requiring mechanical ventilation had a mortality odds ratio of 32.4 (95% confidence interval [CI] 3.1 to 272.0), followed by malignant perforations with 20.2 (95% CI 5.4 to 115.6), a Charlson comorbidity index of 7.1 or greater with 19.6 (95% CI 4.8 to 84.9), the presence of a pulmonary comorbidity with 13.9 (95% CI 2.9 to 97.4), and sepsis with 3.1 (95% CI 1.0 to 10.1). A wait time of greater than 24 hours was not associated with an increased risk of mortality (p=0.52). CONCLUSIONS Malignant perforations, sepsis, mechanical ventilation at presentation, a higher overall burden of comorbidity, and a pulmonary comorbidity have a significant impact on the overall survival. Time to treatment is not as important. Restoration of intestinal continuity, either by primary repair or by excision and reanastomosis can be attempted even in patients with a greater time from perforation to treatment with respectable morbidity and mortality rates.

The results of esophagogastrectomy without thoracotomy for adenocarcinoma of the esophagogastric junction.

Between 1980 and 1988, 98 patients with adenocarcinoma of the esophagogastric junction were seen at the University of Western Ontario. Eighty-two patients underwent resection of the celiac lymph nodes, lesser curve and cardia of the stomach, and thoracic esophagus through abdominal and neck incisions avoiding thoracotomy. The esophagus was replaced by a stomach tube in 80 patients or by a colon tube in two patients. Two of 82 patients died while hospitalized. Early postoperative morbidity included anastomotic leaks that closed spontaneously (13), transient hoarseness (10), myocardial infarction (2), pulmonary embolus (6), and atelectasis or pneumonia (13). Late postoperative complications included delayed gastric emptying (4), symptomatic reflux (4), diarrhea (10), and anastomotic strictures (17). The 2-year survival of 30% was significantly affected by the stage of disease (p = 0.003), depth of tumor penetration (p = 0.02), lymph node metastasis (p = 0.001), tumor differentiation (p = 0.008), and tumor DNA ploidy (p = 0.02). Local recurrences appeared initially in 20 patients: anastomotic (3), peritoneal (14), mediastinal (3); distant metastasis occurred in 27 patients: bone (15), liver (5), brain (2), and multiple organs (5). Swallowing was restored and maintained in 75 patients. Esophagogastrectomy without thoracotomy provides a safe, effective method of restoring swallowing in patients with adenocarcinoma of the esophagogastric junction. This technique provides acceptable survival and local recurrence rates.

Occult Metastases in Lymph Nodes Predict Survival in Resectable Non–Small-Cell Lung Cancer: Report of the ACOSOG Z0040 Trial

PURPOSE The survival of patients with non-small-cell lung cancer (NSCLC), even when resectable, remains poor. Several small studies suggest that occult metastases (OMs) in pleura, bone marrow (BM), or lymph nodes (LNs) are present in early-stage NSCLC and are associated with a poor outcome. We investigated the prevalence of OMs in resectable NSCLC and their relationship with survival. PATIENTS AND METHODS Eligible patients had previously untreated, potentially resectable NSCLC. Saline lavage of the pleural space, performed before and after pulmonary resection, was examined cytologically. Rib BM and all histologically negative LNs (N0) were examined for OM, diagnosed by cytokeratin immunohistochemistry (IHC). Survival probabilities were estimated using the Kaplan-Meier method. The log-rank test and Cox proportional hazards regression model were used to compare survival of groups of patients. P < .05 was considered significant. RESULTS From July 1999 to March 2004, 1,047 eligible patients (538 men and 509 women; median age, 67.2 years) were entered onto the study, of whom 50% had adenocarcinoma and 66% had stage I NSCLC. Pleural lavage was cytologically positive in only 29 patients. OMs were identified in 66 (8.0%) of 821 BM specimens and 130 (22.4%) of 580 LN specimens. In univariate and multivariable analyses OMs in LN but not BM were associated with significantly worse disease-free survival (hazard ratio [HR], 1.50; P = .031) and overall survival (HR, 1.58; P = .009). CONCLUSION In early-stage NSCLC, LN OMs detected by IHC identify patients with a worse prognosis. Future clinical trials should test the role of IHC in identifying patients for adjuvant therapy.