K. Robert Shen

Complete Pathologic Response After Neoadjuvant Chemoradiotherapy for Esophageal Cancer Is Associated With Enhanced Survival

BACKGROUND Neoadjuvant chemoradiotherapy followed by esophagogastrectomy has become the standard of care for patients with locally advanced esophageal cancer. This report analyzes our experience with this treatment approach. METHODS From January 1998 through December 2003, all patients from a single institution receiving neoadjuvant chemoradiotherapy followed by esophagogastrectomy were reviewed for operative mortality, morbidity, long-term survival, and factors affecting survival. Only patients preoperatively staged with both computed tomographic scans and endoscopic ultrasound were included. RESULTS There were 162 patients (142 men, 20 women), and the median age was 61 years (range, 22 to 81 years). Histopathology was adenocarcinoma in 143 patients and squamous cell in 19. Pretreatment clinical stage was II in 28 patients (17%), III in 111 (68%), and IV (M1a) in 23 (14%). Ivor Lewis esophagogastrectomy was the most common procedure, occurring in 132 patients. Operative mortality and morbidity was 4.9% and 37%, respectively. Pathologic response was complete in 42 patients (26%), near complete in 27 (17%), partial in 88 (54%), and unresectable in 5 (3%). Five-year survival for overall, complete, near complete, and partial response patients was 34%, 55%, 27%, and 27%, respectively (p = 0.013). Patients whose lymph nodes were rendered free of cancer showed improved overall and disease-free survival compared with patients having persistently positive lymph nodes (p = 0.019). CONCLUSIONS Esophagogastrectomy after neoadjuvant chemoradiotherapy can be performed with low mortality and morbidity. Patients with complete pathologic response have significantly improved long-term survival compared with patients with near complete and partial responses. Future efforts should be directed at understanding determinants of complete responses.

Surgical Management of Acquired Nonmalignant Tracheoesophageal and Bronchoesophageal Fistulae

BACKGROUND Acquired nonmalignant fistulae between the airway and esophagus (tracheoesophageal fistulae [TEF]) are rare life-threatening conditions. Several management approaches have been proposed, while the optimal strategy remains controversial. METHODS This study is a retrospective review of all patients with TEF treated at our institution from 1978 through 2007. RESULTS Thirty-five patients (22 men, 13 women) underwent surgical repair of acquired nonmalignant TEF. Median age was 55 years (range, 5 to 78). Most common causes were the following: complications of esophageal surgery (11), trauma (6), granulomatous infection (5), stent erosion (4), and prolonged mechanical ventilation (2). Location was proximal trachea in 7, mid-trachea in 5, and distal trachea or bronchus in 23. Fifty-six operations were performed. Six patients had staged repair, with 1 patient requiring 4 operations for recurrent TEF. TEF division and primary repair was performed in 18 patients, esophageal resection with reconstruction in 4, and esophageal diversion in 6. Four patients had suture closure of the esophageal or tracheal defect only, and 3 required segmental tracheal or bronchial resection. Four patients were ventilator dependent at the time of repair. Pedicled tissue flaps were used in 28 patients (80%). Operative mortality was 5.7% (2 of 35). Nineteen patients (54.3%) had complications. Median hospital stay was 14 days (range, 4 to 209). Median follow-up was 30.4 months (range, 0.5 to 233) and complete in 34 (97.1%). Three patients (8.6%) developed recurrent TEF. Twenty-nine patients resumed oral intake. One patient required a permanent tracheal T tube. CONCLUSIONS Single-stage primary repair of both airway and esophageal defects with tissue flap interposition can safely be performed successfully in the majority of patients with acquired nonmalignant TEF.

Mediastinoscopy in Patients With Lung Cancer and Negative Endobronchial Ultrasound Guided Needle Aspiration

BACKGROUND Endobronchial ultrasound with transbronchial needle aspiration (EBUS-TBNA) has been proposed as a safe, less-invasive alternative to mediastinoscopy to stage mediastinal lymph nodes in patients with lung cancer. We evaluated the negative predictive value of EBUS-TBNA in lung cancer patients suspected of having N2 nodal metastases. METHODS This study is a single-institution retrospective review of cases with suspected or confirmed lung cancer undergoing mediastinoscopy after a negative EBUS-TBNA between June 2006 and February 2008. RESULTS A total of 494 patients underwent EBUS-TBNA during the study period. Twenty-nine patients with suspected or confirmed lung cancer had a negative EBUS-TBNA and underwent subsequent mediastinoscopy. Mediastinoscopy was performed for findings suspicious of N2 disease based on noninvasive imaging. Mediastinoscopy found metastatic nodes in eight of 29 patients (28%) for a patient-specific negative predictive value of EBUS-TBNA of 72% (95% CI, 56% to 89%). Mediastinal lymph node dissection found four further patients with positive N2 nodes (19%). The EBUS-TBNA and mediastinoscopy sampled the same lymph node station on 36 occasions in the 29 patients. The average lymph node size was 10 mm. Mediastinoscopy was positive in 5 of 36 stations, for a nodal-specific negative predictive value of EBUS-TBNA of 86% (95% CI, 75% to 97%). CONCLUSIONS Endobronchial ultrasound with transbronchial needle aspiration can effectively sample mediastinal lymph node stations in patients with lung cancer. However, in this early experience, 28% of patients with high clinical suspicion of nodal disease had N2 mediastinal nodal metastases confirmed by mediastinoscopy despite negative EBUS-TBNA.

Is Lymph Node Dissection Required in Pulmonary Metastasectomy for Colorectal Adenocarcinoma

BACKGROUND The aim of this study was to clarify the clinical outcome and significance of mediastinal lymph node dissection (LND) during pulmonary resection of metastases from colorectal adenocarcinoma. METHODS A retrospective chart review was performed. Between April 1985 and December 2009, 518 patients underwent 720 pulmonary metastasectomies for metastatic colorectal adenocarcinoma. Relevant factors were analyzed with the χ2 or Fisher exact test and the Mann-Whitney test. Survival and lymph node (LN) recurrence-free period after pulmonary metastasectomy were analyzed with Kaplan-Meier and Cox proportional hazards methods. RESULTS The overall 5-year and 10-year survival rate after pulmonary metastasectomy were 47.1% and 27.7%, respectively. The only significant prognostic factor for survival after pulmonary metastasectomy was mediastinal LN metastasis (p=0.047 in univariate and 0.0028 in multivariate analysis); 199 patients did not undergo LND, 279 patients underwent LND that were negative, and 40 patients underwent LND that contained 1 or more positive mediastinal LN for metastases. The sensitivity of positron emission tomographic scan for detecting mediastinal LN metastases was only 35%. Although long-term survivors were present, systematic LND was not a significant factor for prolonged survival (p=0.26) in the positive LND group. CONCLUSIONS Mediastinal LN metastases are a significant negative prognostic factor for survival after pulmonary metastasectomy for metastatic colorectal cancer. Computed tomography and positron emission tomography based imaging, as well as preoperative carcinoembryonic antigen levels have poor sensitivity for detecting malignant mediastinal LN in this setting. Systematic mediastinal LND should be performed for prognostic purposes during pulmonary metastasectomy for colorectal metastases.

An alternative postoperative pathway reduces length of hospitalisation following oesophagectomy

OBJECTIVE As part of our ongoing quality improvement effort, we evaluated our conventional approach to post-oesophagectomy management by comparing it to an alternative postoperative management pathway. METHODS Medical records from 386 consecutive patients undergoing oesophagectomy with gastric conduit for oesophageal cancer or Barretts oesophagus with high-grade dysplasia were analysed retrospectively (July 2004 to August 2008). The conventional pathway involved a routine radiographic contrast swallow study at 5-7 days after oesophagectomy with initiation of oral intake if no leak was detected. In the alternative pathway, a feeding jejunostomy was placed for enteral feeding and used exclusively until oral intake was gradually initiated at home at 4 weeks after oesophagectomy. No contrast swallow was obtained in the alternative pathway group unless indicated by clinical suspicion of an anastomotic leak. Each group was analysed on an intention-to-treat basis with respect to anastomotic leak rates, length of hospitalisation, re-admission and other complications. RESULTS A total of 276 (72%) patients underwent conventional postoperative management, 110 (28%) followed the alternative pathway. Patient characteristics were similar in both the groups. The anastomotic leak rate was lower in the alternative pathway with three clinically significant leaks (2.7%) versus 33 in the conventional pathway (12.0%; p=0.01). Among patients undergoing a radiographic contrast swallow examination, a false-negative rate of 5.8% was observed. The swallow study of 14 patients (5.9%) was complicated by aspiration of oral contrast. Postoperatively, 7.3% of patients suffered from pneumonia. There were no significant differences overall in postoperative pulmonary or cardiac complications associated with either pathway. Median length of hospitalisation was 2 days shorter for the alternative pathway (7 days) than the conventional pathway (9 days; p<0.001). There was no significant difference in unplanned re-admission rates. CONCLUSION An alternative postoperative pathway following oesophagectomy involving delayed oral intake and avoidance of a routine contrast swallow study is associated with a shortened length of hospitalisation without a higher risk of complication after hospital discharge.

A Comprehensive Review of Anastomotic Technique in 432 Esophagectomies

BACKGROUND Little consensus exists and varying outcomes are reported when the 4 most common esophagogastric anastomotic techniques are compared: circular stapled (CS), hand sewn (HS), linear stapled (LS) (longitudinally stapled anastomosis), and modified Collard (MC) (combined linear and transverse stapled anastomosis). This report analyzes outcomes of these anastomotic techniques. METHODS From July 2004 through December 2008, all intrathoracic and cervical esophagogastric anastomoses at our institution were reviewed. RESULTS There were 432 patients (358 men, 74 women) who underwent primary esophagogastric operations. Median age was 64 years (range, 23-90 years). The approach was an Ivor Lewis esophagectomy in 254 patients (59%), transhiatal esophagectomy in 115 patients (27%), McKeown (3-hole) esophagectomy in 49 (11%) patients, minimally invasive esophagectomy in 9 (2.1%) patients, and thoracoabdominal esophagectomy in 6 (1.4%) patients. There were 268 intrathoracic (62%) and 164 cervical (38%) anastomoses. Anastomotic techniques included LS in 260 (60%) patients MC in 67 (16%) patients, HS in 57 (13%) patients, and CS in 48 (11%) patients. Operative mortality was 3.7%. Anastomotic leak occurred in 50 patients (11%). Grade III or IV leaks occurred in 21 patients (4.9%), including 13 in the chest (4.8%) and 8 in the neck (4.9%). Grade III or IV leaks occurred in 12 patients (4.6%) with LS anastomoses, in 4 (7.0%) patients with HS anastomoses, in 3 (6.2%) patients with CS anastomoses, and in 2 (3.0%) patients with MC anastomoses. HS anastomoses had the highest odds of leakage (p=0.01) and LS anastomoses had the lowest risk of stricture (p=0.006). CONCLUSIONS When performing an esophagogastric anastomosis, clinically significant leaks occur with similar frequency in both cervical and intrathoracic locations. The HS technique has the highest leak rate and the LS technique had the lowest rate of stricture formation.

Surgical treatment of metachronous second primary lung cancer after complete resection of non–small cell lung cancer

OBJECTIVE To clarify the perioperative and oncologic outcome of pulmonary resection for a metachronous second primary lung cancer (MSPLC) following resection of an initial non-small cell lung cancer (NSCLC). METHODS Retrospective chart review identified 161 patients (88 men and 73 women) with a median age of 70 years (range, 34-88 years) who underwent pulmonary resection for MSPLC between January 2000 and December 2009. Operative morbidity, mortality, and relevant factors were analyzed with χ(2) test or Fisher exact test and Mann-Whitney U test. Survival was analyzed with Kaplan-Meier and Cox proportional hazard method. RESULTS The median interval between the initial and subsequent resection for MSPLC was 42.7 months (range, 7-205 months). There was no operative mortality and postoperative complication rate was 29%. In multivariate analysis, ipsilateral operation (P = .0002) and a lower predicted preoperative percent forced expiratory volume in the first second (P = .0035) were significant risk factors for postoperative complications. Five-year overall survival rates after resection of the initial and second metachronous NSCLC were 87.4% and 60.8%, respectively. Significant negative long-term prognostic factors for survival following resection of a MSPLC in multivariate analysis were tumor size >2 cm (P = .003) and number of pack years of smoking (P = .005). Metastatic nodal disease (P = .19) or a sublobar resection (P = .17) were not associated with worse survival. CONCLUSIONS Surgical treatment of a MSPLC can be undertaken with 5-year survival rate of 60%. Expected operative morbidity and mortality are comparable to primary surgery. Tumors 2 cm or smaller are associated with improved survival and freedom from recurrence. Close long-term follow-up of patients who have undergone resection of NSCLC is recommended.

Hiatal hernia after esophagectomy: analysis of 2,182 esophagectomies from a single institution.

BACKGROUND Esophageal resection is a complex operation often associated with morbidity. Hiatal hernia after esophagectomy is an unusual complication. We reviewed our experience with this complication. METHODS From February 1988 through February 2009 we performed 2,182 esophagectomies. Fifteen (0.69%) patients experienced a hiatal hernia. We reviewed our prospective database for demographics, presentation, operative approaches, and outcomes. RESULTS There were 14 men and 1 woman with a mean age of 59 years. Hernia developed after Ivor Lewis approach in 9, transhiatal in 5, and substernal colon interposition in 1. Presenting symptoms included pain in 7 patients, obstructive symptoms in 5, high chest tube output in 2, shortness of breath in 2, diarrhea in 1, and cough with dysphagia in 1. Two patients were asymptomatic. Radiographic studies revealed bowel in the left chest in 11 patients, right chest in 2, bilaterally in 1, and posterior mediastinum in 1. Hernia repair was through the abdomen in 14 patients and left chest in 1. All had reduction of the herniated contents and closure of the defect; 2 required mesh. There was no early mortality. Complications included wound infection, deep venous thrombosis, chylothorax, urinary retention, sacral decubiti, atrial arrhythmias, respiratory failure, and empyema. Mean follow-up was 34 months. Ten patients are still alive. There have been two hernia recurrences. CONCLUSIONS Hiatal hernia after esophagectomy is rare. Repair can be accomplished with low mortality; however, there is substantial morbidity. Because of the increased risk of incarceration or strangulation, these herniae should be repaired. Long-term outcome is usually excellent.

N2 Disease in T1 Non-Small Cell Lung Cancer

BACKGROUND The optimal management strategy for mediastinal staging in early-stage non-small cell lung cancer (NSCLC) is not clearly defined. The true prevalence of mediastinal lymph node metastases (N2 disease) in resected pathologic T1 (pT1) NSCLC must be known to define the role of invasive mediastinal staging in these patients. METHODS Data of patients with pT1 lesions resected at Mayo Clinic between 1998 and 2006 were retrospectively reviewed. Patients with N2 disease were identified from pathology and operative reports. We reviewed demographics, radiologic data, and surgical procedures for those with pathologic T1 N2 NSCLC. RESULTS We identified 968 cases of pT1 lesions, 59 with pN2 disease (6.1%). For those with T1 N2 disease, the primary lung lesion was peripheral in 18 (31%) and central in 41 (69%). Of these, 36 had negative non-invasive mediastinal staging (3.7%) and were incidentally discovered. The most frequently affected lymph node station was 7 in 22 patients (37%), followed by 5,6 in 18 (31%). Mediastinoscopy found positive lymph nodes in 3 of 16 patients (19%) in which it was performed. Overall 5-year survival for pT1 N2 incidentally discovered during mediastinal lymph node dissection at the time of lung resection was 46% (95% confidence interval, 31% to 68%). CONCLUSIONS True pT1 NSCLC harbors a relatively low rate of N2 disease. The rate of occult N2 disease not observed on noninvasive preoperative mediastinal staging is even lower. For patients with T1 NSCLC and negative mediastinal imaging, routine mediastinoscopy results in a low yield of occult N2 disease discovery.

Oncologic Efficacy of Anatomic Segmentectomy in Stage IA Lung Cancer Patients With T1a Tumors

BACKGROUND Segmentectomy provides an anatomic, parenchymal-sparing strategy for patients with limited lung function. Recently, interest has been renewed in segmentectomy for the treatment of early stage lung cancer. METHODS We reviewed the medical records of all patients undergoing segmentectomy from January 1999 through December 2004. Survival curves were estimated using the Kaplan-Meier method. RESULTS There were 113 consecutive patients (58 men, 55 women); median age was 72.5 years (range, 30 to 94 years). Median forced expiratory volume in 1 second was 1.53 L (range, 0.5 L to 3.27 L). Median diffusion capacity of lung for carbon monoxide was 69% predicted (range, 23% to 129%). Significant comorbidities were present in 62 patients (55%). There was no perioperative mortality. Major morbidity occurred in 28 patients (25%). Mean tumor size was 2.1 cm. Resection margins were negative in all cases. Ninety-two patients (81%) were stage I. Overall 5-year survival was 79% for stage IA patients. Current smoking, diffusion capacity of lung for carbon monoxide less than 69%, tumor size greater than 2 cm, N2 disease, and advanced histology grade were associated with decreased survival by univariate analysis. In a multivariate model, only tumor size greater than 2 cm remained significant. Tumor recurrence was observed in 39 patients (35%): local in 17 patients (15%) and distant only in 22 (20%). For stage IA patients with T1a lesions, local recurrence was 5% and distant recurrence was 13%. Five-year recurrence-free survival of these patients was 69%. CONCLUSIONS Pulmonary segmentectomy can be performed safely in selected patients with preoperative reduced lung function and comorbidities. For stage IA disease, survival approximates that seen after lobectomy, with similar local recurrence rates for patients with T1a tumors.