Rebecca P. Petersen

Thoracoscopic Lobectomy Is a Safe and Versatile Procedure: Experience With 500 Consecutive Patients

Objective:Advantages of thoracoscopic lobectomy for early stage non-small cell lung cancer (NSCLC), as compared with lobectomy by conventional thoracotomy, include less postoperative pain and shorter length of hospitalization. The outcomes after thoracoscopic lobectomy in patients with more complex pulmonary conditions are analyzed to determine safety, efficacy, and versatility. Methods:A prospective database of 500 consecutive patients who underwent thoracoscopic lobectomy between June 1999 and January 2006 was queried. Demographic, histopathologic, perioperative, and outcome variables were assessed using standard descriptive statistics and Kaplan-Meier survival analyses. Results:Thoracoscopic lobectomy was successfully performed in 492 patients (conversion rate, 1.6%). Pathologic analysis included primary NSCLC in 416 patients (83.2%), centrally located secondary pulmonary malignancy in 37 patients (7.4%), and a variety of benign conditions in 45 patients (9%). Among the 416 patients with NSCLC, pathologic analysis demonstrated stage I in 330 patients (55.3%), stage II in 40 patients (9.6%), and stage III or greater NSCLC in 44 patients (10.6%). The operative and perioperative (30-day) mortality was 0% and 1%, respectively. The overall 2-year survival rate for the entire cohort was 80%, and the 2-year overall survival rates for stage I NSCLC, stage II or greater NSCLC, secondary pulmonary malignancy, and granulomatous disease patients were 85%, 77%, 73%, and 89%, respectively. Conclusions:Thoracoscopic lobectomy is applicable to a spectrum of malignant and benign pulmonary disease and is associated with a low perioperative morbidity and mortality rate. Survival rates are comparable to those for lobectomy with thoracotomy.

Tumor infiltrating Foxp3+ regulatory T-cells are associated with recurrence in pathologic stage I NSCLC patients

Early stage lung cancer has a variable prognosis, and there are currently no markers that predict which patients will recur. This study examined the relation between tumor‐regulatory T (Treg) cells and total tumor‐infiltrating T‐cell lymphocytes (TIL) to determine whether they correlated with recurrence.

Thoracoscopic lobectomy is associated with lower morbidity compared with thoracotomy

OBJECTIVES Advantages of thoracoscopic lobectomy include less postoperative pain, shorter hospitalization, and improved delivery of adjuvant chemotherapy. The incidence of postoperative complications has not been thoroughly assessed. This study analyzes morbidity after lobectomy to compare the thoracoscopic approach and thoracotomy. METHODS By using a prospective database, the outcomes of patients who underwent lobectomy from 1999-2009 were analyzed with respect to postoperative complications. Propensity-matched groups were analyzed based on preoperative variables and stage. RESULTS Of the 1079 patients in the study, 697 underwent thoracoscopic lobectomy, and 382 underwent lobectomy by means of thoracotomy. In the overall analysis thoracoscopic lobectomy was associated with a lower incidence of atrial fibrillation (P = .01), atelectasis (P = .0001), prolonged air leak (P = .0004), transfusion (P = .0001), pneumonia (P = .001), sepsis (P = .008), renal failure (P = .003), and death (P = .003). In the propensity-matched analysis based on preoperative variables, when comparing 284 patients in each group, 196 (69%) patients who underwent thoracoscopic lobectomy had no complications versus 144 (51%) patients who underwent thoracotomy (P = .0001). In addition, thoracoscopic lobectomy was associated with a lower incidence of atrial fibrillation (13% vs 21%, P = .01), less atelectasis (5% vs 12%, P = .006), fewer prolonged air leaks (13% vs 19%, P = .05), fewer transfusions (4% vs 13%, P = .002), less pneumonia (5% vs 10%, P = .05), less renal failure (1.4% vs 5%, P = .02), shorter chest tube duration (median of 3 vs 4 days, P < .0001), and shorter length of hospital stay (median of 4 vs 5 days, P < .0001). CONCLUSIONS Thoracoscopic lobectomy is associated with a lower incidence of major complications, including atrial fibrillation, compared with lobectomy by means of thoracotomy. The underlying factors responsible for this advantage should be analyzed to improve the safety and outcomes of other thoracic procedures.

Randomized Multicenter Trial of Hyperthermic Isolated Limb Perfusion With Melphalan Alone Compared With Melphalan Plus Tumor Necrosis Factor: American College of Surgeons Oncology Group Trial Z0020

PURPOSE To determine in a randomized prospective multi-institutional trial whether the addition of tumor necrosis factor alpha (TNF-alpha) to a melphalan-based hyperthermic isolated limb perfusion (HILP) treatment would improve the complete response rate for locally advanced extremity melanoma. PATIENTS AND METHODS Patients with locally advanced extremity melanoma were randomly assigned to receive melphalan or melphalan plus TNF-alpha during standard HILP. Patient randomization was stratified according to disease/treatment status and regional nodal disease status. RESULTS The intervention was completed in 124 patients of the 133 enrolled. Grade 4 adverse events were observed in 14 (12%) of 129 patients, with three (4%) of 64 in the melphalan-alone arm and 11 (16%) of 65 in the melphalan-plus-TNF-alpha arm (P = .0436). There were two toxicity-related lower extremity amputations in the melphalan-plus-TNF-alpha arm, and one disease progression-related upper extremity amputation in the melphalan-alone arm. There was no treatment-related mortality in either arm of the study. One hundred sixteen patients were assessable at 3 months postoperatively. Sixty-four percent of patients (36 of 58) in the melphalan-alone arm and 69% of patients (40 of 58) in the melphalan-plus-TNF-alpha arm showed a response to treatment at 3 months, with a complete response rate of 25% (14 of 58 patients) in the melphalan-alone arm and 26% (15 of 58 patients) in the melphalan-plus-TNF-alpha arm (P = .435 and P = .890, respectively). CONCLUSION In locally advanced extremity melanoma treated with HILP, the addition of TNF-alpha to melphalan did not demonstrate a significant enhancement of short-term response rates over melphalan alone by the 3-month follow-up, and TNF-alpha plus melphalan was associated with a higher complication rate.

Prognostic Factors for Recurrence After Pulmonary Resection of Colorectal Cancer Metastases

BACKGROUND This study was undertaken to review a large series of resections of colorectal pulmonary metastases in the era of modern chemotherapy. METHODS A retrospective chart review of prospectively maintained thoracic surgery databases identified 378 patients who underwent pulmonary resection for colorectal cancer metastases with curative intent from 1998 to 2007. RESULTS The primary site of disease was rectum (52%), left colon (26%), right colon (16%), and unknown (6%). Before thoracic recurrence, 166 patients (44%) had previously undergone resection of extrathoracic metastases. Median disease-free interval (DFI) was 24 months from the time of the primary operation. The number of metastatic deposits resected was one in 60%, two in 20%, three in 10%, and four or more in 10%. Chemotherapy was administered to 87 patients (23%) before resection and to 169 patients (45%) after resection. Three-year recurrence-free survival was 28%, and 3-year overall survival was 78%. Multivariable analysis revealed age younger than 65 years, female sex, DFI less than 1 year, and number of metastases greater than three as independent predictors of recurrence. Of 44 patients with three or more lesions and less than 1 year DFI, none was cured by operation. By contrast, recurrence-free survival was 49% at 3 years for those with one lesion and DFI greater than 1 year. CONCLUSIONS Age younger than 65 years, female sex, DFI less than 1 year, and number of metastases greater than three predict recurrence. Medical management alone should be considered standard for patients who have both three or more pulmonary metastases and less than 1 year DFI.

Marginal Cardiac Allografts Do Not Have Increased Primary Graft Dysfunction in Alternate List Transplantation

Background— Clinical success with modern heart transplantation (HT) has led to the development of an alternate list (AL) HT strategy, matching marginal cardiac allografts with recipients who do not meet standard criteria for HT. Marginal allografts may be at an increased risk for primary graft dysfunction (PGD), the leading cause of early mortality after HT.1 The incidence of PGD in AL HT relative to standard list (SL) HT has not been evaluated, and may contribute to the greater mortality associated with AL HT.2 The objective of this study was to determine the incidence of and predictors for PGD. Methods and Results— A retrospective analysis was performed on 260 consecutive adult patients undergoing either SL HT (n=207) or AL HT (n=53) at our institution from 1/2000 to 1/2005. PGD was defined by requirement for mechanical circulatory support immediately post-HT or more broadly as the need for either mechanical support or high-dose inotrope (epinephrine ≥0.07 &mgr;g/kg/min). Donor hearts allocated to AL recipients were turned down for SL HT for reasons that included coronary disease, left ventricular dysfunction or hypertrophy, and high-dose inotropic requirement. AL HT recipients were significantly older, with a higher proportion of diabetes mellitus and ischemic cardiomyopathy. Both groups experienced a similar incidence of significant rejection, but overall mortality was higher in the AL HT group.2 The incidence of PGD did not differ between AL and SL HT recipients. Pre-transplant VAD and prolonged total ischemic times (≥4.5hours) were independent predictors of PGD. Conclusion— Select marginal donor hearts used in AL HT do not have an increased incidence of PGD. Pre-transplant VAD and prolonged ischemic times are more important determinants of PGD. These data support continued aggressive utilization of marginal donor hearts in AL HT.

Pathologic nodal status predicts disease-free survival after neoadjuvant chemoradiation for gastroesophageal junction carcinoma

BackgroundThe incidence of carcinoma of the gastroesophageal junction (GEJ) is rapidly increasing, and the prognosis remains poor. We examined outcomes in patients who received neoadjuvant chemoradiation for GEJ tumors to identify factors that predict disease-free (DFS) and overall (OS) survival.MethodsA retrospective analysis was performed of 101 consecutive patients who received chemoradiation and surgery for GEJ carcinoma between 1992 and 2001.ResultsThe median DFS and OS of all patients were 16 and 25 months, respectively. Twenty-eight patients with a complete histological response (T0N0) experienced greater DFS compared with all others (P = .02). Node-negative patients, regardless of T stage, experienced improved median DFS (24 months) compared with N1 patients (9 months; P = .01). Preoperative stage, age, tumor location, or Barrett’s esophagus did not independently predict OS by univariate analysis. Multivariate analysis demonstrated that only posttreatment nodal status (P = .03)—not the degree of primary tumor response—predicted DFS.ConclusionsThe nodal status of patients with GEJ tumors after neoadjuvant therapy is predictive of DFS after resection. The poor outcome in node-positive patients supports postneoadjuvant therapy nodal staging, because surgical aggressiveness should be tempered by the realization that cure is unlikely and median survival is short.

Retraction: Genomic signatures to guide the use of chemotherapeutics

The authors wish to retract this article because they have been unable to reproduce certain crucial experiments showing validation of signatures for predicting response to chemotherapies, including docetaxel and topotecan.

Pepsin detection in patients with laryngopharyngeal reflux before and after fundoplication

BackgroundSome patients with gastroesophageal reflux disease (GERD) suffer from laryngopharyngeal reflux (LPR). There is no reliable diagnostic test for LPR as there is for GERD. We hypothesized that detection of pepsin (a molecule only made in the stomach) in laryngeal epithelium or sputum should provide evidence for reflux of gastric contents to the larynx, and be diagnostic of LPR. We tested this hypothesis in a prospective study in patients with LPR symptoms undergoing antireflux surgery (ARS).MethodsNine patients undergoing ARS for LPR symptoms were studied pre- and postoperatively using a clinical symptom questionnaire, laryngoscopy, 24-h pH monitoring, biopsy of posterior laryngeal mucosa, and sputum collection for pepsin Western blot assay.ResultsThe primary presenting LPR symptom was hoarseness in six, cough in two, and globus sensation in one patient. Pepsin was detected in the laryngeal mucosa in eight of nine patients preoperatively. There was correlation between biopsy and sputum (+/+ or −/−) in four of five patients, both analyzed preoperatively. Postoperatively, pH monitoring improved in all but one patient and normalized in five of eight patients. Eight of nine patients reported improvement in their primary LPR symptom (six good, two mild). Only one patient (who had negative preoperative pepsin) reported no response to treatment of the primary LPR symptom. Postoperatively, pepsin was detected in only one patient.ConclusionsPepsin is often found on laryngeal epithelial biopsy and in sputum of patients with pH-test-proven GERD and symptoms of LPR. ARS improves symptoms and clears pepsin from the upper airway. Detection of pepsin improves diagnostic accuracy in patients with LPR.

Erratum: Genomic signatures to guide the use of chemotherapeutics (Nature Medicine (2006) 12 (1294-1300))

The authors wish to retract this article because they have been unable to reproduce certain crucial experiments showing validation of signatures for predicting response to chemotherapies, including docetaxel and topotecan.