Lung volume reduction surgery is safe and leads to functional improvement in patients who fail or cannot undergo bronchoscopic lung volume reduction.

Background: Bronchoscopic lung volume reduction (BLVR) has supplanted surgery in the treatment of patients with advanced emphysema, but not all patients qualify for it. Our study aimed to investigate the outcomes of lung volume reduction surgery (LVRS) among patients who either failed BLVR or were not candidates for it. Methods: We conducted a retrospective analysis of patients who underwent LVRS for upper lobe-predominant emphysema at a single tertiary center between March 2018 and December 2022. The main outcomes measures were preoperative and postoperative respiratory parameters, perioperative morbidity, and mortality. Results: A total of 67 LVRS recipients were evaluated, including 10 who had failed prior valve placement. The median patient age was 69 years, and 35 (52%) were male. All procedures were performed thoracoscopically, with 36 patients (53.7%) undergoing bilateral LVRS. The median hospital length of stay was 7 days (interquartile range, 6-11 days). Prolonged air leak (>7 days) occurred in 20 patients. There was one 90-day mortality from a nosocomial pneumonia (non-COVID-related) and no further deaths at 12 months. There were mean improvements of 10.07% in forced expiratory volume in 1 second and 4.74% in diffusing capacity of the lung for carbon monoxide, along with a mean decrease 49.2% in residual volume (P < .001 for all). The modified Medical Research Council dyspnea scale was improved by 1.84 points (P < .001). Conclusions: LVRS can be performed safely in patients who are not candidates for BLVR and those who fail BLVR and leads to significant functional improvement. Long-term follow-up is necessary to ensure the sustainability of LVRS benefits in this patient population.

Targeting inflammatory factors for chemoprevention and cancer interception to tackle malignant mesothelioma.

Mesothelioma is an incurable cancer of the mesothelial lining often caused by exposure to asbestos. Asbestos-induced inflammation is a significant contributing factor in the development of mesothelioma, and genetic factors also play a role in the susceptibility to this rapidly progressive and treatment-resistant malignancy. Consequently, novel approaches are urgently needed to treat mesothelioma and prevent or reduce the overall incidence of this fatal disease. In this research perspective, we review the current state of chemoprevention and cancer interception progress in asbestos-induced mesothelioma. We discuss the different preclinical mouse models used for these investigations and the inflammatory factors that may be potential targets for mesothelioma prevention. Preliminary studies with naturally occurring phytochemicals and synthetic agents are reviewed. Results of previous clinical chemoprevention trials in populations exposed to asbestos and considerations regarding future trials are also presented.

The International Association for the Study of Lung Cancer Pleural Mesothelioma Staging Project: Proposal for Revision of the TNM Stage Groupings in the Forthcoming (Ninth) Edition of the TNM Classification for Pleural Mesothelioma.

INTRODUCTION: The eighth edition of the TNM classification of pleural mesothelioma (PM) saw substantial changes in T and N components and stage groupings. The International Association for the Study of Lung Cancer collected data into a multinational database to further refine this classification. This ninth edition proposal incorporates changes proposed in the clinical (c)T component but not the pathologic T component, to include size criteria, and further refines TNM stage groupings for PM. METHODS: Data were submitted through electronic data capture or batch transfer from institutional databases. Survival was measured from diagnosis date. Candidate stage groups were developed using a recursive partitioning and amalgamation algorithm applied to all cM0 cases for clinical stage and subsequently for pathologic stage. Cox models were developed to estimate survival for each stage group. RESULTS: Of 3598 submitted cases, 2192 were analyzable for overall clinical stage and 445 for overall pathologic stage. Recursive partitioning and amalgamation generated survival tree on overall survival outcomes restricted to cM0, with newly proposed (ninth edition) cT and cN component-derived optimal stage groupings of stage I (T1N0), II (T1N1; T2N0), IIIA (T1N2; T2N1/2; any T3), IIIB (any T4), and IV (any M1). Although cT and pathologic T descriptors are different in the ninth edition, aligning pathologic stage groupings with clinical stage produced better discrimination than did retaining eighth edition pathologic stage groupings. CONCLUSIONS: To our knowledge, this revision of the clinical TNM classification for PM is the first to incorporate the measurement-based proposed changes in cT category. The pathologic TNM aligns with clinical TNM.

Genomic profiling of tissue and blood predicts survival outcomes in patients with resected pleural mesothelioma.

PURPOSE: Pleural mesothelioma (PM) is an aggressive tumor still considered incurable, in part due to the lack of predictive biomarkers. Little is known about the clinical implications of molecular alterations in resectable PM tissues and blood. Here, we characterized genetic alterations to identify prognostic and predictive biomarkers in patients with resected PM. EXPERIMENTAL DESIGN: Targeted next-generation sequencing was performed in retrospective pleural tumor tissue and paired plasma samples from stage IB-IIIB resected PM. Association between prognosis and presence of specific mutations was validated in silico. RESULTS: Thirty PM tissues and paired blood samples from 12 patients were analyzed. High tissue tumor mutational burden (TMB) (>10 mutations/Mb), tissue median minor allele frequency (MAF) (>9 mutations/Mb), and blood TMB (>6 mutations/Mb), tissue KMT2C, PBRM1, PKHD1,EPHB1 and blood LIFR mutations correlated with longer disease-free survival and/or overall survival. High concordance (>80%) between tissue and blood was found for some mutations. CONCLUSIONS: Tissue TMB and MAF, blood TMB, and specific mutations correlated with outcomes in patients with resected PM and should be further studied to validate their role as prognostic biomarkers and potentially predictive factors for combinations with immune-checkpoint inhibitors. This suggest that molecular profiling could identify longer survivors in patients with resected PM.

Mediastinal Mass, Cancer, or Infection, Atypical Paraesophageal Actinomycosis Infection, Clinical and Surgical Approach.

Actinomyces israelii (AI) is a Gram-positive, rod-shaped bacterium that lives commensally on and within humans as a typical colonizer within the gastrointestinal tract, including the mouth. As an opportunistic pathogen, infection often results from tissue injury or breach of the mucosal barrier (ie, during various dental or GI procedures, aspiration, or specific pathologies such as diverticulitis). Symptoms generally present slowly as a non-tender, indurated mass that evolves into multiple abscesses, fistulae, or draining sinus tracts without regard for anatomical barriers, including fascial planes or lymphatic drainage. However, it may also present as an acute suppurative infection with pain and rapid progression to abscess formation.

Pneumothorax in acute respiratory distress syndrome on extracorporeal membrane oxygenation support.

INTRODUCTION: Pneumothorax is associated with poor prognosis in patients with acute respiratory distress syndrome (ARDS). We sought to examine the outcomes of patients who are supported on veno-venous extracorporeal membrane oxygenation (VV ECMO) and develop a pneumothorax. METHODS: We retrospectively reviewed all adult VV ECMO patients supported for ARDS between 8/2014-7/2020 at our institution, excluding patients with recent lung resection and trauma. Clinical outcomes were compared between patients with a pneumothorax to those without a pneumothorax. RESULTS: Two hundred eighty patients with ARDS on VV ECMO were analyzed. Of those, 213 did not have a pneumothorax and 67 did. Patients with a pneumothorax had a longer duration of ECMO support (30 days [16-55] versus 12 [7-22], p < 0.001) and hospital length of stay (51 days [27-93] versus 29 [18-49], p < 0.001), and lower survival-to-discharge (58.2% versus 77.5%, p = 0.002) compared to patients without a pneumothorax. Controlling for age, BMI, sex, RESP score and pre-ECMO ventilator days, the odds ratio of survival-to-discharge was 0.41 (95% CI 0.22-0.78) in patients with a pneumothorax compared to those without. There was a lower incidence of significant bleeding when chest tubes were placed by proceduralist services (2.4% versus 16.2%, p = 0.03). Removal of the chest tube prior to ECMO decannulation compared to removal after decannulation was associated with need for replacement (14.3% versus 0%, p = 0.01). CONCLUSION: Patients who develop a pneumothorax and are supported with VV ECMO for ARDS have longer duration on ECMO and decreased survival. Further studies are needed to assess risk factors for development of pneumothorax in this patient population.

Laying the Foundation for a Mesothelioma Patient Registry: Development of Data Collection Tools.

Mesothelioma, a cancer of mesothelial cells that line the chest, lungs, heart, and abdomen, is a relatively rare disease. In the United States, approximately 3000 individuals are diagnosed with mesothelioma annually. The primary risk factor for mesothelioma is occupational asbestos exposure which can occur decades prior to disease development, though in approximately 20% of cases, known asbestos exposure is lacking. While several other countries have developed mesothelioma registries to collect key clinical and exposure data elements to allow better estimation of incidence, prevalence, and risk factors associated with disease development, no national mesothelioma registry exists in the U.S. Therefore, as part of a larger feasibility study, a patient exposure questionnaire and a clinical data collection tool were created using a series of key informant interviews. Findings suggest that risk factor and clinical data collection via an on-line questionnaire is feasible, but specific concerns related to confidentiality, in the context of employer responsibility for exposure in the unique U.S. legal environment, and timing of enrollment must be addressed. Lessons learned from piloting these tools will inform the design and implementation of a mesothelioma registry of national scope.

Mesothelioma cancer cells are glutamine addicted and glutamine restriction reduces YAP1 signaling to attenuate tumor formation.

Glutamine addiction is an important phenotype displayed in some types of cancer. In these cells, glutamine depletion results in a marked reduction in the aggressive cancer phenotype. Mesothelioma is an extremely aggressive disease that lacks effective therapy. In this study, we show that mesothelioma tumors are glutamine addicted suggesting that glutamine depletion may be a potential therapeutic strategy. We show that glutamine restriction, by removing glutamine from the medium or treatment with inhibitors that attenuate glutamine uptake (V-9302) or conversion to glutamate (CB-839), markedly reduces mesothelioma cell proliferation, spheroid formation, invasion, and migration. Inhibition of the SLC1A5 glutamine importer, by knockout or treatment with V-9302, an SLC1A5 inhibitor, also markedly reduces mesothelioma cell tumor growth. A relationship between glutamine utilization and YAP1/TEAD signaling has been demonstrated in other tumor types, and the YAP1/TEAD signaling cascade is active in mesothelioma cells and drives cell survival and proliferation. We therefore assessed the impact of glutamine depletion on YAP1/TEAD signaling. We show that glutamine restriction, SLC1A5 knockdown/knockout, or treatment with V-9302 or CB-839, reduces YAP1 level, YAP1/TEAD-dependent transcription, and YAP1/TEAD target protein (e.g., CTGF, cyclin D1, COL1A2, COL3A1, etc.) levels. These changes are observed in both cells and tumors. These findings indicate that mesothelioma is a glutamine addicted cancer, show that glutamine depletion attenuates YAP1/TEAD signaling and tumor growth, and suggest that glutamine restriction may be useful as a mesothelioma treatment strategy.

In vivo spectroscopic evaluation of human tissue optical properties and hemodynamics during HPPH-mediated photodynamic therapy of pleural malignancies.

Significance: Dosimetry for photodynamic therapy is dependent on multiple parameters. Critically, in vivo tissue optical properties and hemodynamics must be determined carefully to calculate the total delivered light dose. Aim: Spectroscopic analysis of diffuse reflectance measurements of tissues taken during a clinical trial of 2-(1-hexyloxyethyl)-2-devinyl pyropheophorbide-a-mediated photodynamic therapy for pleural malignancies. Approach: Diffuse reflectance measurements were taken immediately before and after photodynamic therapy. Measurements were analyzed with a nonlinearly constrained multiwavelength, multi-distance algorithm to extract tissue optical properties, tissue oxygen saturation, StO2, and total hemoglobin concentration (THC). Results: A total of 25 patients were measured, 23 of which produced reliable fits for optical property extraction. For all tissue types, StO2 ranged through [24, 100]% and [22, 97]% for pre-photodynamic therapy (PDT) and post-PDT conditions, respectively. Mean THC ranged through [ 69,152 ] µM and [ 48,111 ] µM, for pre-PDT and post-PDT, respectively. Absorption coefficients, µa, ranged through [ 0.024 , 3.5 ] cm - 1 and [ 0.039 , 3 ] cm - 1 for pre-PDT and post-PDT conditions, respectively. Reduced scattering coefficients, µs', ranged through [ 1.4 , 73.4 ] cm - 1 and [ 1.2 , 64 ] cm - 1 for pre-PDT and post-PDT conditions, respectively. Conclusions: There were similar pre- and post-PDT tissue optical properties and hemodynamics. The high variability in each parameter for all tissue types emphasizes the importance of these measurements for accurate PDT dosimetry.

Chronic Obstructive Pulmonary Disease and Lung Cancer: A Review for Clinicians.

Chronic obstructive pulmonary disease (COPD) and lung cancer are common global causes of morbidity and mortality. Because both diseases share several predisposing risks, the 2 diseases may occur concurrently in susceptible individuals. The diagnosis of COPD has important implications for the diagnostic approach and treatment options if lesions concerning for lung cancer are identified during screening. Importantly, the presence of COPD has significant implications on prognosis and management of patients with lung cancer. In this monograph, we review the mechanistic linkage between lung cancer and COPD, the impact of lung cancer screening on patients at risk, and the implications of the presence of COPD on the approach to the diagnosis and treatment of lung cancer. This manuscript succinctly reviews the epidemiology and common pathogenetic factors for the concurrence of COPD and lung cancer. Importantly for the clinician, it summarizes the indications, benefits, and complications of lung cancer screening in patients with COPD, and the assessment of risk factors for patients with COPD undergoing consideration of various treatment options for lung cancer.

Transglutaminase 2 enhances hepatocyte growth factor signaling to drive the mesothelioma cancer cell phenotype.

Transglutaminase 2 (TG2) is an important mesothelioma cancer cell survival protein. However, the mechanism whereby TG2 maintains mesothelioma cell survival is not well understood. We present studies showing that TG2 drives hepatocyte growth factor (HGF)-dependent MET receptor signaling to maintain the aggressive mesothelioma cancer phenotype. TG2 increases HGF and MET messenger RNA and protein levels to enhance MET signaling. TG2 inactivation reduces MET tyrosine kinase activity to reduce cancer cell spheroid formation, invasion and migration. We also confirm that HGF/MET signaling is a biologically important mediator of TG2 action. Reducing MET level using genetic methods or treatment with MET inhibitors reduces spheroid formation, invasion and migration and this is associated with reduced MEK1/2 and ERK1/2. In addition, MEK1/2 and ERK1/2 inhibitors suppress the cancer phenotype. Moreover, MET knockout mesothelioma cells form 10-fold smaller tumors compared to wild-type cells and these tumors display reduced MET, MEK1/2, and ERK1/2 activity. These findings suggest that TG2 maintains HGF and MET levels in cultured mesothelioma cells and tumors to drive HGF/MET, MEK1/2, and ERK1/2 signaling to maintain the aggressive mesothelioma cancer phenotype.

Limited Left Thoracoscopic Sympathectomy Effectively Silences Refractory Electrical Storm.

BACKGROUND: An electrical storm (ES) is a life-threatening condition that affects up to 20% of patients with implantable cardioverter defibrillators. In this small retrospective study, we report our results with left video-assisted thoracoscopic sympathectomy/ganglionectomy (VATSG) to treat refractory ES in low-ejection fraction patients who were not candidates for catheter ablation. METHODS: We identified 12 patients who presented with ES and underwent a total of 14 video-assisted thoracoscopic sympathectomy/ganglionectomy, including 3 patients on venoarterial extracorporeal membrane oxygenation. We reviewed demographic data, survival to discharge, number of cardioversions (before and after VATSG), need for readmissions, and need for right-sided procedures. RESULTS: In the 30 days before a left VATSG, mean number of shocks was 22.67 for all patients. For the patients who survived to discharge, the mean was 3.55 since surgery and the median was zero shocks after a median follow-up of 358 days. Six patients did not experience further cardioversions since the last VATSG and 5 were not readmitted for ventricular tachycardia. Two patients had staged bilateral procedures owing to recurrences; of those, 1 did not require further cardioversions. CONCLUSIONS: Limited left VATSG is an appropriate and effective initial treatment for ES patients who are not candidates for catheter ablation, including those on venoarterial extracorporeal membrane oxygenation for hemodynamic support.

Examining the impact of physical function performance in predicting patient outcomes after lung-sparing surgery for malignant pleural mesothelioma.

PURPOSE: The purpose of this study was to examine the impact of physical function performance and pulmonary function on patient outcomes after lung-sparing surgery for malignant pleural mesothelioma (MPM). MATERIALS AND METHODS: A retrospective review of 54 patients with MPM from 2015 to 2020 was performed. The primary objective was to assess whether physical function, as measured by the Eastern Cooperative Oncology Group Performance Status (ECOG), and pulmonary function tests were predictive of postoperative patient outcomes (ventilator days, chest tube days, hospital length of stay). A secondary objective was to explore demographic and preoperative variables that best predict postoperative physical function and patient outcomes. RESULTS: Data include 54 patients who underwent extended pleurectomy-decortication. Preoperative ECOG was a significant predictor of postoperative patient outcomes while preoperative lung function lacked predictive ability. Preoperative ECOG was also predictive of preoperative lung function. Age on the day of surgery was the best predictor of postoperative physical function, which was significantly reduced postoperatively. CONCLUSIONS: Preoperative physical function performance was a significant predictor of postoperative outcomes. The results of our study highlight the importance of physical function in patients with MPM and support the need for early rehabilitation and further research to determine optimal rehabilitation interventions.IMPLICATIONS FOR REHABILITATIONPreoperative physical function can predict outcomes after lung-sparing surgery for malignant pleural mesothelioma (MPM).Physical function in patients with MPM should be carefully examined.To accurately reflect patients' abilities, patient assessment should include both patient-reported outcomes and performance-based measures.Patients with MPM should receive rehabilitation early after diagnosis and throughout the continuum of care.

ACTL6A suppresses p21Cip1 tumor suppressor expression to maintain an aggressive mesothelioma cancer cell phenotype.

Mesothelioma is a poor prognosis cancer of the mesothelial lining that develops in response to exposure to various agents including asbestos. Actin-Like Protein 6A (ACTL6A, BAF53a) is a SWI/SNF regulatory complex protein that is elevated in cancer cells and has been implicated as a driver of cancer cell survival and tumor formation. In the present study, we show that ACTL6A drives mesothelioma cancer cell proliferation, spheroid formation, invasion, and migration, and that these activities are markedly attenuated by ACTL6A knockdown. ACTL6A expression reduces the levels of the p21Cip1 cyclin-dependent kinase inhibitor and tumor suppressor protein. DNA binding studies show that ACTL6A interacts with Sp1 and p53 binding DNA response elements in the p21Cip1 gene promoter and that this is associated with reduced p21Cip1 promoter activity and p21Cip1 mRNA and protein levels. Moreover, ACTL6A suppression of p21Cip1 expression is required for maintenance of the aggressive mesothelioma cancer cell phenotype suggesting that p21Cip1 is a mediator of ACTL6A action. p53, a known inducer of p21Cip1 expression, is involved ACTL6A in regulation of p21Cip1 in some but not all mesothelioma cells. In addition, ACTL6A knockout markedly reduces tumor formation and this is associated with elevated tumor levels of p21Cip1. These findings suggest that ACTL6A suppresses p21Cip1 promoter activity to reduce p21Cip1 protein as a mechanism to maintain the aggressive mesothelioma cell phenotype.

Sulforaphane inhibits PRMT5 and MEP50 function to suppress the mesothelioma cancer cell phenotype.

Mesothelioma is a highly aggressive cancer of the mesothelial lining that is caused by exposure to asbestos. Surgical resection followed by chemotherapy is the current treatment strategy, but this is marginally successful and leads to drug-resistant disease. We are interested in factors that maintain the aggressive mesothelioma cancer phenotype as therapy targets. Protein arginine methyltransferase 5 (PRMT5) functions in concert with the methylosome protein 50 (MEP50) cofactor to catalyze symmetric dimethylation of key arginine resides in histones 3 and 4 which modifies the chromatin environment to alter tumor suppressor and oncogene expression and enhance cancer cell survival. Our studies show that PRMT5 or MEP50 loss reduces H4R3me2s formation and that this is associated with reduced cancer cell spheroid formation, invasion, and migration. Treatment with sulforaphane (SFN), a diet-derived anticancer agent, reduces PRMT5/MEP50 level and H4R3me2s formation and suppresses the cancer phenotype. We further show that SFN treatment reduces PRMT5 and MEP50 levels and that this reduction is required for SFN suppression of the cancer phenotype. SFN treatment also reduces tumor formation which is associated with reduced PRMT5/MEP50 expression and activity. These findings suggest that SFN may be a useful mesothelioma treatment agent that operates, at least in part, via suppression of PRMT5/MEP50 function.

Serum soluble mesothelin-related protein (SMRP) and fibulin-3 levels correlate with baseline malignant pleural mesothelioma (MPM) tumor volumes but are not useful as biomarkers of response in an immunotherapy trial.

OBJECTIVES: Soluble mesothelin-related protein (SMRP) and fibulin-3 serum levels may serve as diagnostic and prognostic biomarkers of malignant pleural mesothelioma (MPM). Here, we evaluate these markers for correlation to tumor volume, prognosis and response assessment in a clinical trial of immunogene therapy in combination with chemotherapy. MATERIALS AND METHODS: Serial serum levels of SMRP and fibulin-3 were measured in adult patients with biopsy-proven MPM enrolled in two prospective clinical trials. Pre-therapy computed tomography (CT) measurements of tumor burden were calculated and correlated with pre-therapy serum SMRP and fibulin-3 levels in these two trials. Serological data were also correlated with radiological assessment of response using Modified RECIST criteria over the first 6 months of intrapleural delivery of adenovirus-IFN alpha (Ad.IFN-α) combined with chemotherapy. RESULTS: A cohort of 58 patients who enrolled in either a photodynamic therapy trial or immunotherapy clinical trial had available imaging and SMRP serological data for analysis of whom 45 patients had serological fibulin-3 data. The cohort mean total tumor volume was 387 cm3 (STD 561 cm3). Serum SMRP was detectable in 57 of 58 patients (mean 3.8 nM, STD 6.0). Serum fibulin-3 was detected in 44 of 45 patients (mean 23 ng/mL, STD 14). At pre-therapy baseline in these two trials, there was a strong correlation between tumor volume and serum SMRP levels (r = 0.61, p < 0.001), and a moderate correlation between tumor volume and serum fibulin-3 levels (r = 0.36, p = 0.014). Twenty-eight patients in the immunotherapy trial had longitudinal serologic and radiographic data. Fold-changes in SMRP and fibulin-3 did not show significant correlations with modified RECIST measurements. CONCLUSIONS: Although our data show correlations of SMRP and fibulin-3 with initial tumor volumes as measured by CT scanning, the use of SMRP and fibulin-3 as serological biomarkers in the immunotherapy trial were not useful in following tumor response longitudinally.

Quantitation and predictors of short-term mortality following extrapleural pneumonectomy, pleurectomy/decortication, and nonoperative management for malignant pleural mesothelioma.

BACKGROUND: For malignant pleural mesothelioma (MPM), the benefit of resection, as well as the optimal surgical technique, remain controversial. In efforts to better refine patient selection, this retrospective observational cohort study queried the National Cancer Database in an effort to quantify and evaluate predictors of 30- and 90-day mortality between extrapleural pneumonectomy (EPP) and pleurectomy/decortication (P/D), as well as nonoperative management. METHODS: After applying selection criteria, cumulative incidences of mortality by treatment paradigm were graphed for the unadjusted and propensity-matched populations, as well as for six a priori age-based intervals (≤60, 61-65, 66-70, 71-75, 76-80, and ≥81 years). The interaction between age and hazard ratio (HR) for mortality between treatment paradigms was also graphed. Cox multivariable analysis ascertained factors independently associated with 30- and 90-day mortality. RESULTS: Of 10,723 patients, 2,125 (19.8%) received resection (n=438 EPP, n=1,687 P/D) and 8,598 (80.2%) underwent nonoperative management. The unadjusted 30/90-day mortality for EPP, P/D, and all operated cases was 3.0%/8.0%, 5.4%/14.1%, and 4.9%/12.8%, respectively. There were no short-term mortality differences between EPP and P/D following propensity-matching, within each age interval, or between age subgroups on interaction testing (P>0.05 for all). Nonoperative patients had a crude 30- and 90-day mortality of 9.9% and 24.6%, respectively. Several variables were identified as predictors of short-term mortality, notably patient age (HR 1.022, P<0.001), Charlson-Deyo comorbidity index (HR 1.882, P<0.001), receipt of treatment at high-volume centers (HR 0.834, P=0.032) and induction chemotherapy (HR 1.735, P=0.025), among others. The patient (yearly) incremental increase in age conferred 2.0% (30 day) and 2.2% (90 day) increased risk of mortality (P<0.001). CONCLUSIONS: Quantitative estimates of age-associated 30- and 90-day mortality of EPP and P/D should be considered when potentially operable patients are counseled regarding the risks and benefits of resection.