Minimally invasive esophagectomy: results of a prospective phase II multicenter trial-the eastern cooperative oncology group (E2202) study.

OBJECTIVE: The primary aim of this trial was to assess the feasibility of minimally invasive esophagectomy (MIE) in a multi-institutional setting. BACKGROUND: Esophagectomy is an important, potentially curative treatment for localized esophageal cancer, but is a complex operation. MIE may decrease the morbidity and mortality of resection, and single-institution studies have demonstrated successful outcomes with MIE. METHODS: We conducted a multicenter, phase II, prospective, cooperative group study (coordinated by the Eastern Cooperative Oncology Group) to evaluate the feasibility of MIE. Patients with biopsy-proven high-grade dysplasia or esophageal cancer were enrolled at 17 credentialed sites. Protocol surgery consisted of either 3-stage MIE or Ivor Lewis MIE. The primary end point was 30-day mortality. Secondary end points included adverse events, duration of hospital-stay, and 3-year outcomes. RESULTS: Protocol surgery was completed in 95 of the 104 patients eligible for the primary analysis (91.3%). The 30-day mortality in eligible patients who underwent MIE was 2.1%; perioperative mortality in all registered patients eligible for primary analysis was 2.9%. Median intensive care unit and hospital stay were 2 and 9 days, respectively. Grade 3 or higher adverse events included anastomotic leak (8.6%), acute respiratory distress syndrome (5.7%), pneumonitis (3.8%), and atrial fibrillation (2.9%). At a median follow-up of 35.8 months, the estimated 3-year overall survival was 58.4% (95% confidence interval: 47.7%-67.6%). Locoregional recurrence occurred in only 7 patients (6.7%). CONCLUSIONS: This prospective multicenter study demonstrated that MIE is feasible and safe with low perioperative morbidity and mortality and good oncological results. This approach can be adopted by other centers with appropriate expertise in open esophagectomy and minimally invasive surgery.

Strategies of Well-being Training and Resilience.

As cardiothoracic surgeons, we face frequent challenges to our well-being and our ability to function as our best selves. Building personal resilience is an important way to help us manage these challenges. Here, the authors outline the scope of the problem, the consequences of burnout, and offer 4 strategies to train ourselves to be more resilient: (1) Pursuit of fulfillment, (2) Cultivation of community and belonging, (3) Mitigation of microstresses and avoiding feelings of overwhelm, and (4) Building a "resilience bank account."

Assessment of the well-being of significant others of cardiothoracic surgeons.

OBJECTIVES: We aimed to evaluate how the current working climate of cardiothoracic surgery and burnout experienced by cardiothoracic surgeons influences their spouses and significant others (SOs). METHODS: A 33-question well-being survey was developed by the American Association for Thoracic Surgery Wellness Committee and distributed by e-mail to the SOs of cardiothoracic surgeons and to all surgeon registrants of the 2020 and 2021 American Association for Thoracic Surgery Annual Meetings with a request to share it with their SO. The 5-item Likert-scale survey questions were dichotomized, and associations were determined by χ2 or independent samples t tests, as appropriate. RESULTS: Responses from 238 SOs were analyzed. Sixty-six percent reported that the stress on their cardiothoracic surgeon partner had a moderate to severe influence on their family, and 63% reported that their partner's work demands didn't leave enough time for family. Fifty-one percent reported that their partner rarely had time for intimacy, 27% reported poor work-life balance, and 23% reported that interactions at home were usually or always not good-natured. SOs were most affected when their partner was <5 years out from training, worked in private vs academic practice, and worked longer hours. Having children, particularly younger than age 19 years, and a lack of workplace support resources further diminished well-being. CONCLUSIONS: The current work culture of cardiothoracic surgeons adversely affects their SOs, and the risk for families is concerning. These data present a major area for exploration as we strive to understand and mitigate the factors that lead to burnout among cardiothoracic surgeons.

Esophageal stenting and radiotherapy: a multimodal approach for the palliation of symptomatic malignant dysphagia.

BACKGROUND: Esophageal stents provide immediate palliation of malignant dysphagia; however, radiotherapy (RT) is a superior long-term option. We review the outcomes of combined esophageal stenting and RT for patients with malignant dysphagia. METHODS: We retrospectively reviewed patients with esophageal stents placed for palliation of malignant dysphagia from esophageal stricture, esophageal extrinsic compression, or malignant tracheoesophageal fistula (TEF). We excluded patients with radiation-induced TEF in the absence of tumor. We analyzed and compared outcomes between patients with no RT, RT before stent placement, and RT after stent placement. RESULTS: We placed stents in 45 patients for esophageal stricture from esophageal cancer (n = 30; 66.7 %), malignant TEF (n = 8; 17.7 %), and esophageal compression from airway, mediastinal, or metastatic malignancies (n = 7; 15.6 %). Twenty patients (44.4 %) had no RT; 25 patients had RT before stent placement (n = 16; 35.6 %), RT after stent placement (n = 8; 17.8 %), or both (n = 1; 2.2 %). Median follow-up was 30 days. Complications requiring stent revision were similar with or without RT. Subjective symptom relief was achieved in 68.9 % of all patients, with no differences noted between groups (p = 0.99). The 30-day mortality was 15.6 %. Patients with RT after stent placement had a longer median survival compared to those without RT (98 vs. 38 days). CONCLUSIONS: Esophageal stent placement with RT is a safe approach for malignant dysphagia.

T1/T2 non-small-cell lung cancer treated by lobectomy: does tumor anatomic location matter?

BACKGROUND: The effect of tumor location on long-term survival after lobectomy for stage I non-small-cell lung cancer is unclear. Current data are limited to a retrospective single-institution series. We sought to determine if tumor anatomic location (i.e., the particular lobe that was involved) confers a survival advantage based on population-based data. METHODS: Using the Surveillance, Epidemiology and End Results database (1988-2007), we identified patients who underwent lobectomy for pathologic T1/T2 adenocarcinoma or squamous cell carcinomas. Wedge resections, segmentectomies, and pneumonectomies were excluded. We evaluated the association between the particular lobe that was involved, lymph node (LN) yield, and survival using the Kaplan-Meier method. To adjust for potential confounders, we used a Cox proportional hazards regression model. RESULTS: We identified 13,650 patients who met our inclusion criteria. There were significant differences in unadjusted overall (P=0.03) and cancer-specific survivals (P=0.03) based on tumor location. However, after adjusting for patient factors, geographic location of treatment, and tumor characteristics, we found that tumor location was not associated with significant differences in survival. We found that male gender, black race, squamous cell histology, increasing grade, and age were independent negative predictors of survival. Higher LN yields were independently associated with improved survival. Although adjusted survival rates were not significantly different, there were significant differences (P<0.0001) in LN yield based on tumor location; right middle lobe had the lowest yield (5.1 nodes), and left upper lobe had the highest yield (eight nodes). CONCLUSIONS: LN counts are independent predictors of survival. Although it is associated with significant difference in LN yield, tumor location is not an independent predictor of survival. Age, race, gender, tumor size, histology, and grade appear to be more important prognostic factors. These data suggest that treatment of T1/T2 non-small-cell lung cancer should be dictated by the same oncologic principles, regardless of tumor location.

The long-term impact of surgical complications after resection of stage I nonsmall cell lung cancer: a population-based survival analysis.

OBJECTIVE: Surgical morbidity may influence long-term cancer survival. Because resection of early stage nonsmall cell lung cancer (NSCLC) is primary therapy, we sought to determine the survival impact of surgical complications for elderly patients undergoing resection of stage I NSCLC. METHODS: Using the linked Surveillance Epidemiology and End Results-Medicare database (2000-2005), we identified elderly patients who underwent lobectomy for stage I NSCLC. We then assessed the unadjusted association between in-hospital, postoperative complications, and long-term survival for patients who survived more than 30 days after resection using the Kaplan-Meier method. Finally, we used Cox proportional hazards regression to evaluate the relationship between postoperative complications and 5-year cancer-specific (CSS) and overall survival (OS) after adjusting for patient, tumor, and treatment characteristics. RESULTS: We identified 3996 eligible patients. The overall in-hospital, postoperative complication rate was 54.2%. Pulmonary complications were the most common (n = 1464) followed by cardiac (n = 916). Unadjusted 5-year CSS was significantly worse for those who had an in-hospital, postoperative complication (70.9%) compared to those who did not (78.9%, P < 0.001). OS was also significantly worse (P < 0.001) for patients who developed a complication. Complications continued to predict worse 5-year CSS and OS after adjusting for patient, tumor, and treatment characteristics (HR: 1.38, 95% CI, 1.17-1.64). CONCLUSIONS: The occurrence of in-hospital postoperative complications was an independent predictor of worse 5-year CSS after resection of stage I NSCLC. Importantly, the impact of surgical complications extends well after the initial perioperative period. These findings may help identify important targets for best practice guidelines and quality-of-care measures.

Being an effective surgical educator.

Training in thoracic surgical residencies has evolved in the past several years, with significant advances in simulation technology, heightened pressure regarding work-hour reforms, and initiation of integrated training programs. This article highlights current concepts in surgical education and methods of incorporating teaching opportunities into practice. General strategies on how to be a better teacher and increase student feedback evaluation scores are addressed. Finally, the evolving roles and responsibilities of a mentor in assisting residents and colleagues in developing successful thoracic surgical careers are explored.

The Resilience Bank Account: Skills for Optimal Performance.

The day-to-day life of a cardiothoracic surgeon and other high-stakes occupations is riddled with chronic stress punctuated by acute, sometimes life-threatening, crises. Additional stress from the realms of a surgeon's personal life can add to the silent burden surgeons often carry. The tolls paid for poor management of the cumulative stress load can impact surgeons and their patients, leading to errors of clinical judgment, burnout, early departures from practice, health issues, and substance abuse. This article reviews 6 individual skills or habits that can, when proactively integrated into a daily routine, make the difference. The idea of investing in a resilience bank account is suggested as a metaphor for the reserve building and cumulative positive impact of these habits over time.

Minimally invasive versus open Roux-en-Y gastric bypass: effect on immune effector cells.

BACKGROUND: Minimally invasive surgery (MIS) has several potential benefits compared with the open approach, including potentially less perioperative immunosuppression. Data characterizing the differential stress responses have been limited to serum cytokine analyses and animal studies. We hypothesized that the open approach to Roux-en-Y gastric bypass (RYGB) has a more deleterious, negative, quantifiable effect on the peripheral blood mononuclear cells than does the MIS approach. METHODS: Patients undergoing open and MIS RYGB for morbid obesity had blood samples collected preoperatively and postoperatively on days 1 and 2 and at the first follow-up visit. The peripheral blood mononuclear cells were isolated and analyzed for phenotype using flow cytometry, natural killer cell cytotoxicity using 51-chromium release assay, and gene expression using Affymetrix U133 Plus 2.0 microarray. RESULTS: Patient age and body mass index were similar between the 2 groups. Postoperatively, differences within the open group were seen for CD3+/CD16- (T lymphocytes), CD3-/CD16+ (natural killer cells), CD3+/CD4+ (T-helper lymphocytes), and CD4/CD8 subsets (P<.05). No differences were seen within the open group CD3+/CD8+ (cytotoxic T lymphocytes) or within the MIS subsets. Between the 2 approaches, no phenotypic differences were found, except for the postoperative day 1 CD3+/CD16- (P<.05). Within each group, significant decreases were found in cytotoxicity on days 1 and 2 compared with preoperatively (P<.05). The cytotoxicity seen after MIS had returned to the preoperative levels at the first follow-up visit, but the cytotoxicity after open RYGB had not (P<.05). Between the 2 groups, the open group had greater cytotoxic decreases than did the MIS group at postoperative days 1 and 2 (P<.05). Microarray analysis of the preoperative (n=20) and day 2 (n=20) specimens identified a 20-gene signature that correlated with the surgical approach. CONCLUSION: Open RYGB surgery causes greater inhibition of innate immunity than does MIS. This inhibition was not accounted for by phenotypic changes. Gene expression changes from surgical stress might represent the molecular basis of this differential immune response.

Gemcitabine and metabolite pharmacokinetics in advanced NSCLC patients after bronchial artery infusion and intravenous infusion.

PURPOSE: We investigated the safety, pharmacokinetics, and efficacy of gemcitabine administered via bronchial artery infusion (BAI) and IV infusion in advanced NSCLC patients. METHODS: Patients were eligible if they had received at least two prior cytotoxic chemotherapy regimens. Gemcitabine was administered via BAI as 600 mg/m2 on day one of cycle one, followed by IV as 1000 mg/m2 on day eight of cycle one, and IV on days one and eight of all subsequent cycles. Pharmacokinetics for gemcitabine and dFdU metabolite in plasma, and dFdCTP active metabolite in peripheral blood mononuclear cells (PBMC) were evaluated. Intensive pharmacokinetic sampling was performed after BAI and IV infusions during cycle one. RESULTS: Three male patients (age range 59-68 years) were evaluated. All patients responded with stable disease or better. One PR was observed after cycle three, and the remaining had SD. Cmax (mean ± SD) following BAI for gemcitabine, dFdCTP, and dFdU were 7.71 ± 0.13, 66.5 ± 40.6, and 38 ± 6.27 µM and following IV infusion, 17 ± 2.36, 50.8 ± 3.61, and 83.2 ± 12.3 µM, respectively. The AUCinf (mean ± SD) following BAI for gemcitabine, dFdCTP, and dFdU were 6.89 ± 1.2, 791.1 ± 551.2, and 829.9 ± 217.8 µM h and following IV infusion, 12.5 ± 3.13, 584 ± 86.6, and 1394.64 ± 682.2 µM h, respectively. The AUC and Cmax of dFdCTP after BAI were higher than IV. The median OS was 6.27 months. No grade 3 or 4 toxicity was observed. The most common side effects were all grade ≤ 2 involving nausea, vomiting, rigor, thrombocytopenia, and anemia. CONCLUSIONS: Systemic exposure to dFdCTP was higher after BAI than IV in two out of three patients.

Recommendations for optimal use of imaging studies to clinically stage mediastinal lymph nodes in non-small-cell lung cancer patients.

Appropriate clinical staging of mediastinal lymph nodes in non-small-cell lung cancer (NSCLC) patients has important therapeutic and prognostic implications. Because of the wide variations in practice patterns among community and academic physicians, we reviewed the literature so that we could provide evidence-based recommendations on the use of imaging studies in the pretreatment clinical staging of NSCLC patients. We concluded that the most sensitive and accurate method of noninvasive mediastinal nodal staging is a positron emission tomography/computed tomography fusion scan; we believe this tool should be a component of clinical staging of all NSCLC patients. Given insufficient sensitivity with currently available imaging studies, mediastinal nodal staging should also include histologic evaluation.

Radiographic staging of mediastinal lymph nodes in non-small cell lung cancer patients.

In conclusion, accurate pretreatment staging of NSCLC patients is essential so that they undergo the most appropriate treatment. Imaging studies play an integral part in clinical staging. The preferred imaging method for staging the mediastinum is PET/CT, preferably integrated. Until the sensitivity and accuracy of imaging studies are equivalent to the available MLN biopsy techniques, all candidates for definitive therapy require histologic assessment of the mediastinum.

A new approach for treatment of gastro-gastric fistula after gastric bypass.

We report a novel technique for gastro-gastric fistula (GGF) repair. A 44-year-old woman was found to have a fistula between her gastric pouch and bypassed stomach 18 years after Roux-en-Y gastric bypass (RYGBP) for morbid obesity. She underwent an attempted open surgical repair, which was complicated by postoperative abdominal sepsis. An upper gastrointestinal series, abdominal CT scan and upper endoscopy confirmed the diagnosis of failed surgery with recurrent GGF. Under endoscopic and fluoroscopic guidance, two ports were inserted percutaneously into the stomach. The fistula was closed with a percutaneous, transgastric, totally extraperitoneal approach. She remains well 7 months after this intervention. This procedure appears to be a safe and effective minimally invasive approach for closure of GGF after RYGBP. This is the first description of an intragastric, percutaneous closure of a GGF after RYGBP in the medical literature. Further experience with this technique is needed to define the selection criteria, limitations, advantages, and disadvantages.

Thoracoscopic lingulectomy for invasive pulmonary aspergillosis.

Invasive pulmonary aspergillosis (IPA) is associated with a high mortality rate in immunocompromised patients. Surgery has a therapeutic role for selected patients when the main objective is to achieve infection control with minimal lung resection. Large or deep-seated lesions may require an anatomic resection such as segmentectomy, lobectomy, or pneumonectomy. Thoracoscopic lobectomy has been described as a treatment of localized IPA; however, thoracoscopic anatomic segmentectomy has not been reported until now. Herein, we describe a case of thoracoscopic lingulectomy for localized IPA in an immunocompromised patient: this operation minimized the delay in resuming therapy for the patient's underlying acute myeloid leukemia. Video-assisted thoracoscopic segmentectomy can be safely performed for localized IPA.

Open lobectomy for patients with stage I non-small cell lung cancer.

Until additional multi-institutional, randomized, controlled trials provide evidence to the contrary, open lobectomy with mediastinal lymphadenectomy should be considered the gold standard for treating patients with stage I NSCLC with sufficient cardiopulmonary reserve, including older patients. It is the operation with which alternative pulmonary resections, including video-assisted thoracoscopic lobectomy and sublobar resection, should be compared. In treating stage I NSCLC patients, sublobar resection should be reserved for patients with inadequate physiologic reserve to tolerate lobectomy and for those enrolled in clinical trials.

Evolution of clipping for thoracoscopic sympathectomy in symptomatic hyperhidrosis.

BACKGROUND: Severe hyperhidrosis is treated by thoracic sympathetic chain interrupting through chain transection or clipping. Our study compared the efficacy of these 2 methods. METHODS: Retrospectively, patients who underwent thoracoscopic sympathectomy from 1999 to 2005 had demographic, operative, and postoperative data analyzed. RESULTS: Fifty-four operations were performed for refractory sweating of the palm (72%), axilla (66%), foot (53%), and head/neck (19%). Thirty-seven (69%) underwent clipping; 17 (31%) underwent chain transection. There was no difference in age, sex, or blood loss. One ganglion level was interrupted in 24.1% and 2 levels in 75.4%. Bothersome compensatory hyperhidrosis occurred in 13% (5-clipping and 2-transection). One patient underwent clip removal for debilitating symptoms. Three small pneumothoraces occurred (all in the transection group); all treated expectantly. CONCLUSIONS: Thoracoscopic sympathectomy is a safe outpatient procedure. Both methods yield excellent results with minimal compensatory hyperhidrosis. Thoracoscopic sympathetic chain clipping and transection are equivalent.

Anatomic findings and outcomes after antireflux procedures in morbidly obese patients undergoing laparoscopic conversion to Roux-en-Y gastric bypass.

BACKGROUND: To report the anatomic findings and outcomes in patients undergoing laparoscopic takedown of Nissen fundoplication with conversion to Roux-en-Y gastric bypass. METHODS: We reviewed the records of patients who underwent laparoscopic Nissen takedown with conversion to Roux-en-Y gastric bypass from January 2001 to April 2006 at the University of Minnesota Medical Center. RESULTS: Eleven patients were identified. Nine patients had gastroesophageal reflux disease preoperatively, of whom six underwent 24-hour pH monitoring. In 2 patients, the pH study findings were negative. Eight prior procedures had been performed laparoscopically. Eight patients were women. The mean age was 44 years. The average body mass index preoperatively was 44 kg/m(2) (range 35-61). The mean follow-up was 13.8 months (range 4-39). The body mass index at follow-up was 30.2 kg/m(2). The operative time was 349 minutes (range 222-624). The hospital length of stay was 3.4 days (range 2-6). No conversions to open surgery were required. No major short-term complications developed. Minor complications included wound or drain site infection in 3 patients, with abscess in 2, pressure sore of the lateral aspect of the foot in 1, pneumonia in 2, and marginal ulcer in 2 patients. No strictures were observed. One internal hernia occurred. Of the 9 patients with gastroesophageal reflux disease preoperatively, all had 100% improvement in symptoms, with complete resolution in 7 (78%). Wrap disruption was present in 5 (45%) of 11 patients. Herniation of an intact wrap had occurred in 1 patient. One patient had both herniation and wrap disruption. CONCLUSION: Laparoscopic conversion of Nissen fundoplication to Roux-en-Y gastric bypass is a feasible salvage operation for recurrent gastroesophageal reflux disease in the morbidly obese. The incidence of wrap disruption appears to be relatively high and the incidence of intact wrap herniation low in obese patients after failed Nissen fundoplication, suggesting that the mechanism of failure after primary antireflux surgery in obese patients may be different than that in normal-weight patients.

The use of real-time polymerase chain reaction in thoracic malignancies.

Recent progress in the molecular analysis of NSCLC tumors and lymph node status will likely translate into a clearer understanding of the variables and predictors of tumor recurrence. This understanding may lead to more appropriate therapeutic decisions both in the operating room and in the clinic. With these analyses at the molecular level, a more precise molecular classification is on the horizon which includes a molecular substaging. All of these aspects of NSCLC biology await testing or final analysis of prospective multi-institutional trials such as that set forth in CALGB 9761.

Selective activation of insulin receptor substrate-1 and -2 in pleural mesothelioma cells: association with distinct malignant phenotypes.

Molecular mechanisms active in transforming human pleural cells remain incompletely understood. Our previous microarray analysis of malignant pleural mesothelioma revealed alterations in components of the insulin-like growth factor (IGF) system, implicating this signaling axis in tumorigenesis. Therefore, in this current study, we characterized the molecular phenotype and investigated the key signaling pathways of the IGF system in malignant pleural mesothelioma specimens. For the major IGF components, we assessed mRNA abundance and total protein levels. We measured IGF-I ligand-dependent activation of signaling pathways downstream of the type I IGF receptor in a subset of malignant pleural mesothelioma cell lines and determined the corresponding biological consequences. At the transcriptional level, we observed consistent changes in IGF components that may contribute to a malignant phenotype. IGF-I stimulation of cells resulted in enhanced activation of type I IGF receptor and IRS adaptor proteins. Differential activation of IRS-1 signaling was associated with cell growth, whereas IRS-2 signaling was associated with cell motility. Thus, these data suggest that multiple mechanisms likely contribute to malignant pleural mesothelioma tumorigenesis. Therefore, IGF system components represent novel malignant pleural mesothelioma therapeutic targets for investigation.