Richard A. Malthaner

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.

Neoadjuvant or adjuvant therapy for resectable esophageal cancer: a systematic review and meta-analysis.

BackgroundCarcinoma of the esophagus is an aggressive malignancy with an increasing incidence. Its virulence, in terms of symptoms and mortality, justifies a continued search for optimal therapy. The large and growing number of patients affected, the high mortality rates, the worldwide geographic variation in practice, and the large body of good quality research warrants a systematic review with meta-analysis.MethodsA systematic review and meta-analysis investigating the impact of neoadjuvant or adjuvant therapy on resectable thoracic esophageal cancer to inform evidence-based practice was produced.MEDLINE, CANCERLIT, Cochrane Library, EMBASE, and abstracts from the American Society of Clinical Oncology and the American Society for Therapeutic Radiology and Oncology were searched for trial reports.Included were randomized trials or meta-analyses of neoadjuvant or adjuvant treatments compared with surgery alone or other treatments in patients with resectable thoracic esophageal cancer. Outcomes of interest were survival, adverse effects, and quality of life. Either one- or three-year mortality data were pooled and reported as relative risk ratios.ResultsThirty-four randomized controlled trials and six meta-analyses were obtained and grouped into 13 basic treatment approaches.Single randomized controlled trials detected no differences in mortality between treatments for the following comparisons:- Preoperative radiotherapy versus postoperative radiotherapy.- Preoperative and postoperative radiotherapy versus postoperative radiotherapy. Preoperative and postoperative radiotherapy was associated with a significantly higher mortality rate.- Postoperative chemotherapy versus postoperative radiotherapy.- Postoperative radiotherapy versus postoperative radiotherapy plus protein-bound polysaccharide versus chemoradiation versus chemoradiation plus protein-bound polysaccharide.Pooling one-year mortality detected no statistically significant differences in mortality between treatments for the following comparisons:- Preoperative radiotherapy compared with surgery alone (five randomized trials).- Postoperative radiotherapy compared with surgery alone (five randomized trials).- Preoperative chemotherapy versus surgery alone (six randomized trials).- Preoperative and postoperative chemotherapy versus surgery alone (two randomized trials).- Preoperative chemoradiation therapy versus surgery alone (six randomized trials).Single randomized controlled trials detected differences in mortality between treatments for the following comparison:- Preoperative hyperthermia and chemoradiotherapy versus preoperative chemoradiotherapy in favour of hyperthermia.Pooling three-year mortality detected no statistically significant difference in mortality between treatments for the following comparison:- Postoperative chemotherapy compared with surgery alone (two randomized trials).Pooling three-year mortality detected statistically significant differences between treatments for the following comparisons:- Preoperative chemoradiation therapy versus surgery alone (six randomized trials) in favour of preoperative chemoradiation with surgery.- Preoperative chemotherapy compared with preoperative radiotherapy (one randomized trial) in favour of preoperative radiotherapy.ConclusionFor adult patients with resectable thoracic esophageal cancer for whom surgery is considered appropriate, surgery alone (i.e., without neoadjuvant or adjuvant therapy) is recommended as the standard practice.

Cyclosporin versus Tacrolimus as Primary Immunosuppressant After Liver Transplantation: A Meta-Analysis

A systematic review of randomized clinical trials (RCT) was undertaken to evaluate the beneficial and harmful effects of immunosuppression with cyclosporin versus tacrolimus for liver transplanted patients. MEDLINE, EMBASE, Cochrane Central and Hepato‐Biliary Group Controlled Trials Registers were searched. Using fixed and random effects model, relative risk (RR), values <1 favoring tacrolimus, with 95% confidence intervals (CI) were calculated. Of 717 potentially relevant references, 16 RCTs were eligible for inclusion. Mortality and graft loss at 1 year were significantly reduced in tacrolimus‐treated recipients (Death: RR 0.85, 95% CI 0.73–0.99; graft loss: RR 0.73, 95% CI 0.61–0.86). Tacrolimus reduced the number of recipients with acute rejection (RR 0.81, 95% CI 0.75–0.88) and steroid‐resistant rejection (RR 0.54, 95% CI 0.47–0.74) in the first year. Lymphoproliferative disorder or dialysis rates were not different but more de novo diabetes (RR 1.38, 95% CI 1.01–1.86) occurred with tacrolimus. More patients stopped cyclosporin than tacrolimus (RR 0.57, 95% CI 0.49–0.66). Treating 100 recipients with tacrolimus instead of cyclosporin would avoid rejection and steroid‐resistant rejection in nine and seven patients respectively, graft loss and death in five and two patients respectively, but four additional patients would develop diabetes after liver transplantation.

Stapled Hemorrhoidopexy Is Associated with a Higher Long-Term Recurrence Rate of Internal Hemorrhoids Compared with Conventional Excisional Hemorrhoid Surgery

PurposeThe purpose of this systematic review was to compare the long-term results of stapled hemorrhoidopexy with conventional excisional hemorrhoidectomy in patients with internal hemorrhoids.MethodsA systematic review of all randomized, controlled trials comparing stapled hemorrhoidopexy and conventional hemorrhoidectomy with long-term results was performed by using the Cochrane methodology. The minimum follow-up was six months. Primary outcomes were hemorrhoid recurrence, hemorrhoid symptom recurrence, complications, and pain.ResultsTwelve trials were included. Follow-up varied from six months to four years. Conventional hemorrhoidectomy was more effective in preventing long-term recurrence of hemorrhoids (odds ratio (OR), 3.85; 95 percent confidence interval (CI), 1.47–10.07; P < 0.006). Conventional hemorrhoidectomy also prevents hemorrhoids in studies with follow-up of one year or more (OR, 3.6; 95 percent CI, 1.24–10.49; P < 0.02). Conventional hemorrhoidectomy is superior in preventing the symptom of prolapse (OR, 2.96; 95 percent CI, 1.33–6.58; P < 0.008). Conventional hemorrhoidectomy also is more effective at preventing prolapse in studies with follow-up of one year or more (OR, 2.68; 95 percent CI, 0.98–7.34; P < 0.05). Nonsignificant trends in favor of conventional hemorrhoidectomy were seen in the proportion of asymptomatic patients, bleeding, soiling/difficultly with hygiene/incontinence, the presence of perianal skin tags, and the need for further surgery. Nonsignificant trends in favor of stapled hemorrhoidopexy were seen in pain, pruritus ani, and symptoms of anal obstruction/stenosis.ConclusionsConventional hemorrhoidectomy is superior to stapled hemorrhoidopexy for prevention of postoperative recurrence of internal hemorrhoids. Fewer patients who received conventional hemorrhoidectomy complained of hemorrhoidal prolapse in long-term follow-up compared with stapled hemorrhoidopexy.

The Role of Surgery in the Management of Thymoma: A Systematic Review

The literature describing multimodal treatment of thymomas consists almost exclusively of retrospective case series. We have used a systematic review to investigate the role of surgery in the management of thymomas. The use of surgery as the sole therapeutic maneuver in thymoma depends on the stage considered. Subtotal resection followed by adjuvant treatment may prolong survival, but studies are equivocal. Some data supports re-resection of recurrent thymoma in the belief that survival will be prolonged. Approaches to thymectomy other than sternotomy in early stage thymoma are technically sound, but long-term outcome data are lacking.

Robot-assisted Tactile Sensing for Minimally Invasive Tumor Localization

The 10 mm incisions used in minimally invasive cancer surgery prevent the direct palpation of internal organs, making intraoperative tumor localization difficult. A tactile sensing instrument (TSI), which uses a commercially available sensor to measure distributed pressure profiles along the contacting surface, has been developed to facilitate remote tissue palpation. The objective of this research is to assess the feasibility of using the TSI under robotic control to reliably locate underlying tumors while reducing collateral tissue trauma. The performance of humans and a robot using the TSI to locate tumor phantoms embedded into ex vivo bovine livers is compared. An augmented hybrid impedance control scheme has been implemented on a Mitsubishi PA10-7C to perform the force/position control used in the trials. The results show that using the TSI under robotic control realizes an average 35% decrease in the maximum forces applied and a 50% increase in tumor detection accuracy when compared to manual manipulation of the same instrument. This demonstrates that the detection of tumors using tactile sensing is highly dependent on how consistently the forces on the tactile sensing area are applied, and that robotic assistance can be of great benefit when trying to localize tumors in minimally invasive surgery.

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.

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.