Clinical Understaging, Treatment Response, and Survival Among Esophageal Adenocarcinoma Patients.

INTRODUCTION: Selecting appropriate management for patients with esophageal adenocarcinoma (EA) is predicated on accurate clinical staging information. Inaccurate information could lead to inappropriate treatment and suboptimal survival. We investigated the relationship between staging accuracy, treatment, and survival. METHODS: This was a national cohort study of EA patients in the National Cancer Data Base (2006-2015) treated with upfront resection or neoadjuvant therapy (NAT). Clinical and pathological staging information was used to ascertain staging concordance for each patient. For NAT patients, Bayesian analysis was used to account for potential downstaging. We evaluated the association between staging concordance, receipt of NAT, and survival through hierarchical logistic regression and multivariable Cox regression. RESULTS: Among 7635 EA patients treated at 877 hospitals, 3038 had upfront resection and 4597 NAT followed by surgery. Relative to accurately staged patients, understaging was associated with a lower likelihood (odds ratio [OR] 0.04 95% confidence interval [CI] 0.02-0.05) while overstaging was associated with a greater likelihood of receiving NAT (OR 1.98 [1.53-2.56]). Relative to upfront surgery, treatment of cT1N0 patients with NAT was associated with a higher risk of death (HR 3.08 [2.36-4.02]). For accurately or overstaged cT3-T4 patients, NAT was associated with a lower risk of death whether downstaging occurred (ypN0 disease-HR 0.67 [0.49-0.92]; N+ disease-HR 0.55 [0.45-0.66]) or not (ypN + disease-HR 0.78 [95% CI 0.65-0.93]). CONCLUSIONS: Clinical understaging is associated with receipt of NAT which in turn may have a stage-specific impact on patients' survival regardless of treatment response. Guidelines should account for the possibility of inaccurate clinical staging.

Esophageal Adenocarcinoma: Screening, Surveillance, and Management.

Esophageal adenocarcinoma (EAC) is a growing problem with a rapidly rising incidence. Risk factors include gastroesophageal reflux disease, central obesity, and smoking. The prognosis of EAC remains poor because it is usually diagnosed late, and many efforts have been made to improve prevention, early detection, and treatment. Acid suppression, nonsteroidal antiinflammatory drugs (NSAIDs), and statins may play a role in chemoprevention. Screening for Barrett's esophagus (BE), the only known precursor lesion of EAC, is indicated for individuals with increased risk. Endoscopic surveillance of patients with BE likely improves overall outcomes. Endoscopic ablation and resection is highly effective for treating dysplastic BE and early EAC, whereas esophagectomy is indicated for patients with locally advanced disease. This review covers epidemiology, staging, screening, and prevention of EAC as well as endoscopic and surgical management.

Utility of Adjuvant Chemotherapy After Neoadjuvant Chemoradiation and Esophagectomy for Esophageal Cancer.

OBJECTIVE: To determine whether adjuvant chemotherapy (AC) after neoadjuvant chemoradiation and esophagectomy is associated with improved overall survival for patients with locally advanced esophageal cancer, and to evaluate how pathologic disease response to neoadjuvant treatment impacts this effect. BACKGROUND: Neoadjuvant chemoradiation is currently the preferred management approach for locoregional esophageal cancer. Although there is interest in the use of AC, the benefit of systemic therapy after neoadjuvant chemoradiation and esophagectomy is unclear. METHODS: Retrospective cohort study of patients with esophageal cancer treated with neoadjuvant chemoradiation and esophagectomy in the National Cancer Data Base (2006-2012). RESULTS: Among 3592 patients with esophageal cancer (84.7% adenocarcinoma, 15.2% squamous cell carcinoma), 335 (9.3%) were treated with AC. AC was not associated with a significantly lower risk of death among patients with no residual disease (ypT0N0) or residual non-nodal disease (ypT+N0). Among patients with residual nodal disease (ypTanyN+), AC was associated with a 30% lower risk of death in the overall cohort [hazard ratio (HR) 0.70, (0.57-0.85)] and among those with adenocarcinoma [HR 0.69 (0.57-0.85)]. Using a 90-day postoperative landmark, findings were similar. Among patients with postoperative length of stay ≤10 days and no unplanned readmission, AC was associated with approximately 40% lower risk of death among patients with residual nodal disease [overall cohort, HR 0.63 (0.48-0.84); adenocarcinoma, HR 0.66 (0.49-0.88)]. CONCLUSIONS: AC after neoadjuvant chemoradiation and esophagectomy is associated with improved survival in patients with residual nodal disease. Our findings suggest AC may provide additional benefit for esophageal cancer patients, and merits further investigation.

Diameter of Solid Tumor Component Alone Should be Used to Establish T Stage in Lung Adenocarcinoma.

PURPOSE: The computed tomographic (CT) appearance of so-called ground glass components within lung adenocarcinomas correlate with noninvasive tumor histology, and solid radiographic components correlate with invasive histology. We hypothesized that T stage might be more accurately applied by considering the solid component nodule diameter rather than total nodule diameter. METHODS: We identified 74 patients with a solitary lung adenocarcinoma who underwent resection without receiving neoadjuvant therapy. Maximum total diameter and solid diameter of the nodules were measured on CT scans performed within 3 months of surgery. Cox proportional hazard modeling and Kaplan-Meier analyses were performed to determine whether total nodule diameter or solid component diameter was more predictive of overall survival. RESULTS: Thirty-three patients (45 %) had a solid nodule and 41 patients (55 %) had a part-solid nodule. Most patients were white (59 %) and female (69 %), and 42 % had never smoked. Seventy-four percent underwent lobectomy and 23 % sublobar resection. Sixty-six percent had pathologic stage I disease, 22 % stage II, and 12 % stage IIIA. Mean ± SD total and solid nodule diameters were 32.1 ± 17.5 and 24.8 ± 18.0 mm, respectively (p = 0.01). Among patients with part-solid nodules, multivariate modeling incorporating significant univariate predictors of survival (age, gender, procedure, N descriptor) revealed that maximum solid diameter was associated with overall survival (hazard ratio 1.4, p = 0.01), while maximum total diameter was not. CONCLUSIONS: In a largely non-Asian cohort undergoing resection for adenocarcinoma, radiographic diameter of the solid component of a part-solid lesion on CT predicts overall survival better than total lesion diameter. These data provide further evidence to support altering the T descriptor for lung adenocarcinoma for part-solid nodules.

Pleurectomy and decortication are associated with better survival for bicavitary cytoreductive surgery for mesothelioma compared with extrapleural pneumonectomy.

OBJECTIVES: Mesothelioma is a nearly uniformly fatal tumor. Multimodality therapy including cytoreductive surgery and chemotherapy is associated with long-term survival in some patients. Cytoreductive surgery for thoracic disease includes a lung-sparing operation called an "extended pleurectomy/decortication" or a lung-sacrificing surgery called an "extrapleural pneumonectomy." The benefit of cytoreductive surgery for bicavitary disease (chest and abdomen) is poorly understood. Our objective was to evaluate the long-term survivals for patients undergoing cytoreductive surgery for bicavitary disease and to determine whether any prognostic factors were associated with outcome. METHODS: We reviewed our Institutional Review Board-approved, institutional, International Association for the Study of Lung Cancer Mesothelioma Staging Project database. Inclusion criteria were all patients who underwent cytoreductive surgery for bicavitary disease. Overall survival was calculated by Kaplan-Meier methodology. All International Association for the Study of Lung Cancer database elements were evaluated by univariable analysis. RESULTS: From February 2014 to August 2021, 440 patients with mesothelioma were evaluated. Fourteen patients (3%) underwent cytoreductive surgery of both chest and abdomen as a planned 2-stage operation. Most patients (13/14; 93%) underwent chest surgery before abdomen surgery. For the entire cohort, the median overall survival was 33.6 months with a 5-year survival of 20%. Extended pleurectomy/decortication was associated with a better outcome compared with extrapleural pneumonectomy, with median overall survivals of 58.2 versus 13.5 months, respectively. CONCLUSIONS: For a highly selected group of patients with bicavitary mesothelioma, long-term survival can be achieved with an aggressive, staged surgical approach. The patients who undergo extended pleurectomy/decortication with preservation of the lung appear to have more favorable outcomes compared with patients undergoing extrapleural pneumonectomy.

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.

Staging Concordance and Guideline-Concordant Treatment for Esophageal Adenocarcinoma.

BACKGROUND: Treatment selection for patients with esophageal adenocarcinoma is predicated on clinical staging information, which is inaccurate in 20% to 30% of cases and could impact the delivery of guideline-concordant treatment. We aimed to evaluate the association between staging concordance at the patient and hospital levels with the delivery of guideline-concordant treatment among esophageal adenocarcinoma patients. METHODS: This was a national cohort study of resected esophageal adenocarcinoma patients in the National Cancer Data Base (2006 to 2015) treated either with upfront resection or neoadjuvant therapy followed by surgery. Patient- and hospital-level clinical and pathologic staging concordance and deviations from treatment guidelines were ascertained. For neoadjuvant therapy patients, staging concordance was predicted through Bayesian analysis. Reliability adjustment was used when evaluating hospital-level concordance. RESULTS: Among 9393 esophageal adenocarcinoma patients treated at 927 hospitals, 41% had upfront surgery. Among upfront surgery patients, staging concordance was 85.1% for T1N0 and 86.9% for T3-T4N+ disease, but less than 50% for all others. Among patients treated with neoadjuvant therapy, treatment downstaging was observed in 33.9%. Deviations from treatment guidelines were identified in 38.5% of upfront surgery patients and 3.3% of neoadjuvant therapy patients. The proportion of concordantly staged patients ranged from 60.1% to 87.9%, and deviations from treatment guidelines were observed among 14.9% to 22.7% of the patients. Patient staging concordance increased, and deviations from guidelines decreased, as hospital-level concordance increased (trend test, P values less than .001 for all). CONCLUSIONS: Deviations from treatment guidelines in esophageal adenocarcinoma patients appear to be a function of inaccurate clinical staging information, which should be a new focus for quality improvement efforts.

Demographic Landscape of Cardiothoracic Surgeons and Residents at United States Training Programs.

BACKGROUND: Recruiting and promoting women and racial/ethnic minorities could help enhance diversity and inclusion in the academic cardiothoracic (CT) surgery workforce. However, the demographics of trainees and faculty at US training programs have not yet been studied. METHODS: Traditional, integrated (I-6), and fast-track (4+3) programs listed in the Accreditation Council for Graduate Medical Education (ACGME) public database were analyzed. Demographics of trainees and surgeons, including gender, race/ethnicity, subspecialty, and academic appointment (if applicable), were obtained from ACGME Data Resource Books, institutional websites, and public profiles. Chi-square and Cochran-Armitage trend tests were performed. RESULTS: In July 2020, 78 institutions had at least 1 CT surgery training program; 40 (51%) had only a traditional program, 20 (26%) traditional and I-6, 6 (8%) all 3 types of program, and 4 (5%) only I-6. The proportion of female trainees increased significantly from 2011 to 2019 (19% vs 24%, P < .001), with female I-6 trainees outnumbering female traditional trainees since 2018. Significant increases by race/ethnicity were observed overall and by program type, notably for Asian and Hispanic individuals in I-6 programs and Black individuals in traditional programs. Finally, of the 1175 CT surgeons identified, 633 (54%) were adult cardiac surgeons, 360 (37%) assistant professors, 116 (10%) women, and 33 (3%) Black. CONCLUSIONS: The demographic landscape of CT surgery trainees and faculty across multiple training pathways reflects increasing representation by gender and race/ethnicity. However, we must continue to work toward equitable representation in the workforce to benefit the diverse patients we treat.

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.

Appendiceal carcinoid tumors: Predictors of lymph node metastasis and the impact of right hemicolectomy on survival.

BACKGROUND AND OBJECTIVES: Given the lack of population-based data in the literature, we sought to (1) identify predictors of appendiceal carcinoid tumor nodal metastasis to distinguish which patients would most likely benefit from hemicolectomy and (2) compare survival after hemicolectomy versus appendectomy alone. METHODS: Using the Surveillance Epidemiology and End Results Database (1988-2005), we identified patients with appendiceal carcinoid tumors who underwent resection. We identified risk factors for nodal metastasis using logistic regression models and used the Kaplan-Meier method to compare adjusted overall and cancer-specific survival after right hemicolectomy versus appendectomy alone. RESULTS: 576 patients met our inclusion criteria. We found that tumor size (>2.0 cm) and tumor histology (pure carcinoid tumors) were significant predictors of lymph node metastasis. After stratifying by tumor size, we did not detect a significant difference in survival between patients who underwent hemicolectomy and those that underwent appendectomy alone (log-rank, P > 0.10). CONCLUSIONS: Tumor size and histology are significant predictors of appendiceal carcinoid tumor nodal metastasis and therefore may be helpful to identify which patients would most likely benefit from a hemicolectomy. However, our population-based study did not demonstrate a significant difference in adjusted survival rates between hemicolectomy versus appendectomy alone.

Diagnostic Laparoscopy Improves Staging of Malignant Pleural Mesothelioma With Routine Positron Emission Tomography Imaging.

BACKGROUND: With a multimodal treatment strategy, cytoreductive surgery extends survival in malignant pleural mesothelioma. Improving the accuracy of staging can refine patient selection. Our objective was to determine whether diagnostic laparoscopy (DL) improves staging for patients with malignant pleural mesothelioma with the routine use of positron emission tomography (PET). METHODS: We performed a retrospective review of our prospectively maintained database from February 2014 to May 2019. Inclusion criteria were patients who had disease in the chest that was deemed potentially resectable by radiographic criteria and who underwent DL as part of the staging evaluation before surgery. RESULTS: Of 187 patients (71% men, 80% epithelial) who underwent DL during staging, 76% proceeded to surgery; 22% were unresectable at exploratory thoracotomy and 78% underwent resection (pleurectomy and decortication, 68%; extrapleural pneumonectomy, 32%). Also, 89% had a PET computed tomography (CT), and 11% had a preoperative CT without PET. DL revealed peritoneal disease in 17%. Among patients with pathologically proven disease at DL, 77% had negative PET-CT imaging. Based on the pathologic findings at DL the sensitivity, specificity, positive predictive value, and negative predictive value of PET-CT were 23%, 78%, 17%, and 83%, respectively. The accuracy of PET-CT was 68%. CONCLUSIONS: PET-CT has low sensitivity and diagnostic accuracy to identify peritoneal disease in malignant pleural mesothelioma. DL as part of the preoperative staging defines an important subset of patients with bicavitary disease. We recommend DL as a component of staging before surgery.

Conditional survival after surgical treatment of melanoma: an analysis of the Surveillance, Epidemiology, and End Results database.

BACKGROUND: Survival curves following surgical treatment of cutaneous melanoma are heavily influenced by early deaths. Therefore, survival estimates may be misleading for long-term cancer survivors. We examined whether conditional survival (CS) is more accurate in predicting long-term melanoma survival. METHODS: We used the Surveillance, Epidemiology, and End Results database (1992-2005) to identify patients who underwent surgical treatment for melanoma. We included patients with T2-T4 disease and with known nodal status. Patients were stratified into low-risk (T2-3N0M0) and high-risk (T4N0M0 or T2-4N1-3M0) categories. We defined CS as time-specific estimates conditioned on living to a certain point in follow-up, and calculated 10-year cancer-specific survival curves conditioned on annual survival. We adjusted for potential confounders using a Cox proportional hazards regression model (alpha = 0.05). RESULTS: A total of 8647 patients met inclusion criteria (low-risk, 5987 [69.2%]; high-risk, 2660 [30.8%]). At diagnosis, low-risk patients had a significantly better 10-year survival rate (low-risk, 79.6%; high-risk, 41.2%; P < 0.001). On CS analysis, survival differences remained until 8 years after treatment, after which 10-year cancer-specific survival rates were no longer significantly different (P = 0.51) for low-risk (95.4%) and high-risk (91.7%) groups. Multivariate analysis demonstrated that age, gender, location, and ulceration (initial predictors of survival) were no longer predictive after 8 years of survival. CONCLUSIONS: For patients who survive 8 years after surgical treatment of melanoma, CS data become discordant with traditionally used estimates. Our findings have important implications for patient counseling, as high-risk melanoma survivors may require no more intensive surveillance than low-risk survivors 8 years after treatment.

Surgery for Locally Advanced and Oligometastatic Non-Small Cell Lung Cancer.

Locally advanced non-small cell lung cancer is a heterogeneous group of tumors that require multidisciplinary treatment. Although there is much debate with regard to their management, a multimodal treatment strategy for carefully selected patients that includes surgery can extend survival compared with nonoperative definitive therapy. As the role of targeted therapies and immune checkpoint inhibitors for these tumors becomes better defined, practices will continue to evolve.

United States Administrative Databases and Cancer Registries for Thoracic Surgery Health Services Research.

BACKGROUND: Data from administrative claims and cancer registries have an ever-expanding role in thoracic surgery health services and health policy research. However, their strengths, limitations, and appropriate applications are often poorly understood, leading to errors in study design and data interpretation. The intent of this review is to discuss relevant and crucial considerations when conducting research with some of the most common national thoracic surgery data sources. METHODS: Information on the National Cancer Database; National Inpatient Sample; American College of Surgeons National Surgical Quality Improvement Project; Surveillance, Epidemiology, and End Results (SEER) Database; SEER-linked databases; The Society of Thoracic Surgery General Thoracic Surgery Database; and state cancer registries were obtained from the official webpages for these databases and from a review of PubMed (1990 to July 1, 2019). RESULTS: We provided a review of the above-mentioned commonly used administrative databases and cancer registries in thoracic surgery health services research, with particular attention toward their strengths and limitations. CONCLUSIONS: An appreciation of the strengths, limitations, and differences between various sources of data from administrative, hospital-based, and population-based cancer registries is equally essential for investigators to improve the quality and accuracy of their research and for readers to properly interpret the results of such studies.

Diaphragmatic eventration.

Symptomatic diaphragmatic eventration is an uncommon condition and is sometimes impossible to distinguish clinically from paralysis. Patients who are asymptomatic require no treatment; patients who are symptomatic benefit significantly from diaphragm plication. The choice of plication approach is dependent upon the expertise of the surgeon.

Prognostic value of neoadjuvant treatment response in locally advanced esophageal adenocarcinoma.

OBJECTIVE: To determine the association between neoadjuvant chemotherapy and chemoradiation therapy on completeness of pathologic response and to assess the impact of primary tumor versus nodal response on survival after esophagectomy. METHODS: Patients aged 18 to 80 years in the National Cancer Data Base (2006-2016) with clinically staged, locally advanced (cT2-4 or cN+) esophageal adenocarcinoma who underwent an R0 esophagectomy after neoadjuvant chemotherapy or chemoradiation therapy were included. Multivariable Cox proportional hazards regression models were constructed to assess the association between treatment response and survival. RESULTS: Among 2870 patients, there was a significant dose-response association between completeness of response and overall survival: no response (reference), partial response (hazard ratio [HR], 0.81; 95% confidence interval [CI], 0.72-0.91), and complete response (HR, 0.55; 95% CI, 0.47-0.65). Compared with neoadjuvant chemotherapy alone, neoadjuvant chemoradiation was associated with higher pathologic primary tumor (33.9% vs 21.3%; P < .001) and pathologic nodal response rates (55.9% vs 32.7%; P < .001). Both a primary and nodal response were associated with improved survival. However, among patients with a primary but no nodal response, primary tumor response was not associated with risk of death (HR, 0.88; 95% CI, 0.69-1.11). In contrast, among patients who had a nodal but no primary response, the survival benefit of a nodal response was maintained (HR, 0.66; 95% CI, 0.58-0.76). CONCLUSIONS: Pathologic nodal (rather than primary tumor) response to neoadjuvant therapy is associated with improved survival. These data suggest a need to optimize neoadjuvant strategies associated with more complete nodal response rates and to consider more aggressive adjuvant treatment for patients with residual nodal disease after esophagectomy.

Utilization of Minimally Invasive Thymectomy and Margin-Negative Resection for Early-Stage Thymoma.

BACKGROUND: Minimally invasive thymectomy (MIT) has demonstrated improved short-term outcomes compared with open thymectomy (OT). Although adoption of MIT for thymoma is increasing, oncologic outcomes have not been well characterized. METHODS: This was a retrospective cohort study of adult patients from the National Cancer Database who underwent MIT or OT for Masaoka stage I to II thymoma between 2010 and 2014. The primary outcome was R0 resection. Secondary outcomes included MIT use, perioperative mortality, and length of stay. RESULTS: Nine hundred forty-three patients from 395 hospitals underwent thymectomy for stage I to II thymoma. MIT was performed in 31.3% (59.7% robotic, 40.3% thoracoscopic). Over the study period MIT utilization increased from 21.0% to 40.2% (trend test, p < 0.001). R0 resection was achieved in 83.1% of MITs (86.6% stage I, 72.7% stage II) and 79% of OTs (85.5% stage I, 65.8% stage II). In multivariable analyses, the likelihood of incomplete resection (R1/2) was associated with stage II tumors (odds ratio, 2.51) and World Health Organization B3 histology (odds ratio, 3.66). R0 resection was not associated with surgical approach (p = 0.17) and did not vary with tumor size (trend test, p = 0.90). Mortality rates at 30 and 90 days were 0% and 0.5%, respectively. MIT was associated with significantly shorter lengths of stay than OT (-1.03 days [95% confidence interval, -1.68 to -0.38]). CONCLUSIONS: The use of MIT for resection of early-stage thymoma is increasing and is not associated with lower rates of R0 resection than OT. Reasons for the relatively low rates of R0 resection among all thymectomies requires further investigation, and long-term outcomes data are needed to better define the oncologic effectiveness of MIT.

Povidone-iodine results in rapid killing of thymic epithelial tumour cells through cellular fixation†.

OBJECTIVES: Hyperthermic pleural lavage with povidone-iodine (PVP-I) is utilized to control micrometastatic disease following cytoreductive surgery for thymic epithelial tumours (TETs). Our objective was to investigate whether PVP-I demonstrates direct cytotoxicity against human TET cells. METHODS: Human Met-5A (immortalized mesothelial cell), IU-TAB-1 (thymoma) and Ty-82 (thymic carcinoma) cell lines were treated with serial dilutions of PVP-I (0.01-10%) for 5, 30 and 60 min at 37°C and 42°C. MTT assays and flow cytometry were used to evaluate cell death and apoptosis. Membrane permeability was assayed by intracellular staining of cleaved poly-ADP-ribose polymerase. Cellular fixation was evaluated by membrane disruption of dead cells by dimethylsulphoxide and by comparing cleaved poly-ADP-ribose polymerase staining following PVP-I with known fixatives. RESULTS: MTT assays demonstrated that PVP-I concentrations greater than 0.5% led to rapid cell death in both TET cell lines regardless of temperature. IC50 values following 5 min of exposure to PVP-I were 8.4 mM (0.3%) and 13.3 mM (0.48%) for IU-TAB-1 and Ty-82, respectively and 8.9 mM (0.32%) for MeT-5A. Flow cytometry demonstrated that 5-min exposure of either cell line to 1% PVP-I resulted in profound cell death: 74% and 58% at 5 min and 97% and 95% at 30 min, for IU-TAB-1 and Ty-82 cells, respectively. Resistance of PVP-I-treated cells to dimethylsulphoxide lysis and similar cleaved poly-ADP-ribose polymerase expression following PVP-I and known fixatives revealed cellular fixation as the mechanism of death following PVP-I exposure. CONCLUSIONS: PVP-I results in rapid death of human TET cells and normal mesothelial cells through a cellular fixation mechanism and may, therefore, favourably impact the control of micrometastatic disease following resection of TETs with pleural dissemination.