Patients with early-stage lung cancers have a high risk of relapse and death even after curative surgery. Detection of circulating tumour DNA (ctDNA) in plasma perioperatively is associated with shorter recurrence free survival (RFS). ctDNA-Lung-Detect is an investigator-initiated prospective study of ctDNA detection and association with RFS in patients with early stage non-small cell lung cancer (NSCLC).

Liquid biopsy is emerging as a complement to tumor tissue profiling in advanced non-small-cell lung cancer (NSCLC) patients. We prospectively evaluated the use of a plasma-first approach in the initial diagnostic work-up of patients with suspected advanced NSCLC (NCT04862924).

Purpose Ex vivo lung perfusion (EVLP) rewarms donor lungs to normothermia following a period of cold static preservation (CIT1) and returns the lungs to a state of cold static preservation following EVLP (CIT2). We hypothesize that EVLP interrupts cold ischemic injury and allows for safe additional cold ischemic time after EVLP. Methods We performed a retrospective review of data from the Toronto Lung Transplant Program Database. Adult patients who underwent bilateral lung transplant following EVLP assessment between January 2008 and December 2020 were included. CIT1, EVLP, and CIT2 times were collected and outcomes including PGD grade 3 at 72 hours and 30-day and 12-month mortality were assessed. Results A total of 1186 bilateral lung transplants were performed over the study period of which 315 were performed following EVLP assessment. Mean[SD] CIT1 of the lungs was 4.7h[1.6]. Mean[SD] EVLP time was 4.5h[1.5]. The first lung had a mean[SD] CIT2 of 3.8h[2.1] and the second had a mean[SD] CIT2 of 6.0h[2.2]. Survival was similar when comparing CIT2<6 hours versus CIT2>6 hours of the second lung (p=0.53) (Figure). PGD3 rate was also similar between those groups (18.1% vs 17.2%, p=1). Conclusion Prolonged (>6h) ischemic time following EVLP assessment (CIT2) did not affect short- and long-term mortality in our patients. Therefore we feel that using a period of CIT after EVLP assessment is acceptable, and it provides us flexibility in terms of logistics, widening geographical reach of our program, and allows us to make lung transplantation a semi-elective procedure.

Though not every SLT with rejected contralateral lung necessitated evaluation by EVLP, the availability of EVLP allowed for additional evaluation of questionable single lungs. This has led to increased utilization rates and improved outcomes of SLT with a rejected contralateral lung in the EVLP era.

Purpose Uncontrolled donation after death by circulatory criteria (uDCD) has the potential to alleviate some of the shortage of suitable lungs for transplantation. Non-Perfused Organ Donors (NPOD) differs from uDCD donors in that only lungs are obtained as no reperfusion is instituted after individuals suffer an unexpected sudden cardiac arrest. Family are approached rapidly by trained coordinators for consent to donate lungs. This study reviews our initial experience and challenges with NPOD donation. Methods Data were collected from donors and recipients involved in NPOD lung transplants between February 2016 and October 2018. We describe NPOD donor volumes, ischemia time, utilization rates, length of intensive care unit (ICU) and hospital stay, and survival. Results There were 101 referrals during this period. Of the 34 approached for donation, consent was obtained in 24 cases, and the lung transplant team evaluated 24 NPOD donors on site. Eleven donors were declined before retrieval because of medically unsuitable lungs, and 4 donors were declined after retrieval due to severe lung injury on site. Nine lungs underwent ex vivo lung perfusion in order to evaluate suitability for transplantation and eventually 3 were used for transplantation. Thus, the total utilization rate from consented donors was 12.5%. The mean warm ischemic time was 160 minutes (range: 106-175 minutes). The mean age of 3 recipients was 48 ± 2.5 years. The 30-day mortality was 0%. One patient bridged to transplantation on extracorporeal membrane oxygenation (ECMO) was kept on ECMO for 5 days after transplant. Median ICU stay was 20 days (range: 5-78 days). Median hospital stay was 47 days (range: 18-100 days). Two out of 3 patients are alive at a median of 716 days (range: 100-936 days) with good performance status and lung function. One patient that was on ECMO prior to transplantation died of multisystem organ failure 100 days after transplantation. Conclusion This study demonstrated the potential for NPOD lung donation. However, utilization rates are low. Therefore, improved strategies of lung preservation before retrieval are required to increase and select lungs that are utilizable for transplantation.

Purpose One of the most promising strategies to increase organ donation is the use of organs from donors with Hepatitis C (HCV). We evaluated the safety of transplanting NAT+HCV donors into non-infected lung recipients. Methods Between Oct 2017 and Oct 2018, NAT+HCV donors in North America were considered. Recipients consented to receive such organs under study protocol NCT03112044. Exclusion criteria included existence of liver disease or multi-organ transplant. Outcomes of study recipients were compared to patients receiving non-infected donors. Primary endpoints were survival and HCV status at 6 months after transplantation. All patients becoming viremic received S/V starting at least 2 weeks after transplantation. Results During the one-year study period 200 lung transplant procedures were performed at our center. Of these, 20 (10%) were from NAT+ HCV donors. Compared to standard donors, HCV donors were significantly younger (33y vs. 52y, p=0.002), more likely to be located in the United States vs. Canada (75% vs 5%, p=0.001), and more likely to be smokers (95% vs. 47%, p=0.0001). Donor P/F ratio (383 mmHg vs. 424 mmHg) and proportion of DCD (10% vs. 27%) were not statistically different between the 2 groups. Recipient age, lung disease, urgency status and positive donor HLA crossmatch were similar between the 2 groups. There was a significantly higher proportion of single lung transplants in the HCV group (55% vs. 15%, p=0.002). Post-transplant time on ventilation, ICU and hospital length of stay, use of ECMO and survival (100% in HCV group) were similar between the 2 groups. All patients, except 1 became viremic within 1 week after transplantation. 12 weeks treatment with S/V started at a median of 21 days after transplantation (range 14-71). All patients achieved negative HCV PCR from 2 to 6 weeks after treatment initiation. Two patients presented with HCV relapse within 3 months after S/V termination. One of the relapses was associated with alteration in liver enzymes. Conclusion Excellent intermediate-term clinical outcomes were achieved using NAT+HCV donors to non-infected recipients and this practice should continue to be encouraged. However, a higher relapse rate (10% to date) than previously reported in non-lung transplant patients was observed and novel strategies aiming at prevention of transmission should be further studied. One of the most promising strategies to increase organ donation is the use of organs from donors with Hepatitis C (HCV). We evaluated the safety of transplanting NAT+HCV donors into non-infected lung recipients. Between Oct 2017 and Oct 2018, NAT+HCV donors in North America were considered. Recipients consented to receive such organs under study protocol NCT03112044. Exclusion criteria included existence of liver disease or multi-organ transplant. Outcomes of study recipients were compared to patients receiving non-infected donors. Primary endpoints were survival and HCV status at 6 months after transplantation. All patients becoming viremic received S/V starting at least 2 weeks after transplantation. During the one-year study period 200 lung transplant procedures were performed at our center. Of these, 20 (10%) were from NAT+ HCV donors. Compared to standard donors, HCV donors were significantly younger (33y vs. 52y, p=0.002), more likely to be located in the United States vs. Canada (75% vs 5%, p=0.001), and more likely to be smokers (95% vs. 47%, p=0.0001). Donor P/F ratio (383 mmHg vs. 424 mmHg) and proportion of DCD (10% vs. 27%) were not statistically different between the 2 groups. Recipient age, lung disease, urgency status and positive donor HLA crossmatch were similar between the 2 groups. There was a significantly higher proportion of single lung transplants in the HCV group (55% vs. 15%, p=0.002). Post-transplant time on ventilation, ICU and hospital length of stay, use of ECMO and survival (100% in HCV group) were similar between the 2 groups. All patients, except 1 became viremic within 1 week after transplantation. 12 weeks treatment with S/V started at a median of 21 days after transplantation (range 14-71). All patients achieved negative HCV PCR from 2 to 6 weeks after treatment initiation. Two patients presented with HCV relapse within 3 months after S/V termination. One of the relapses was associated with alteration in liver enzymes. Excellent intermediate-term clinical outcomes were achieved using NAT+HCV donors to non-infected recipients and this practice should continue to be encouraged. However, a higher relapse rate (10% to date) than previously reported in non-lung transplant patients was observed and novel strategies aiming at prevention of transmission should be further studied.

Continued smoking after a lung cancer diagnosis is associated with poorer outcomes. Tobacco retail availability is negatively associated with cessation in non-cancer patients but this has not been explored in cancer survivors. We evaluated the impact of tobacco retail availability on tobacco cessation in lung cancer survivors. Lung cancer survivors from Princess Margaret Cancer Centre (Toronto, Canada) completed questionnaires at diagnosis and follow-up evaluating changes in tobacco use with a median of 26 months apart. Validated tobacco retail location data were obtained from Ministry of Health and patient home addresses were geocoded using ArcGIS 10.6.1, which calculated walking time/distance to nearest vendor, and vendor density within 250 meters (m) and 500m from patient residences. Multivariable logistic regression and Cox proportional hazard models evaluated the impact of vendor availability on cessation and time to quitting after diagnosis respectively, adjusting for significant clinico-demographic and tobacco covariates. 242/721 lung cancer survivors smoked at diagnosis; subsequent overall quit rate after diagnosis was 66%. Mean distance and walking time to a vendor was 0.8 km (range 0-13) and 10 min (range 0-157). On average, there was one vendor (range 0-19) within 250m and five vendors (range 0-36) within 500m from pts; 40% and 64% of pts lived within 250m and 500m from at least one vendor respectively. Greater distance (aOR 1.28 per 1000m [95% CI 0.97-1.70] p = 0.08) and increased walking time (aOR 1.02 per minute [1.00-1.05] p = 0.08) to a tobacco vendor had a non-significant trend towards increased chances of quitting at one year. Living within 250m (aOR 0.43 [0.25-0.74] p = 0.003) or 500m (aOR 0.50 [0.28-0.88] p = 0.02) to at least one vendor reduced quitting at one year. Living near more vendors within 500m had a non-significant trend towards having an increasing dose effect on reducing cessation rates at one year (aOR 0.97 per vendor [0.94-1.00] p = 0.08). Living within 500m to a vendor reduced chance of quitting at any time (aHR 0.70 [0.50-1.00] p = 0.05). Close proximity to tobacco retail outlets is associated with reduced cessation rates for lung cancer survivors. Reducing density of tobacco vendors is a cessation strategy that could positively impact lung cancer patient outcomes.

Impact on survival in patients with surgically resected multifocal neuroendocrine lesions (MNET), such as diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH) or tumorlets, along with primary typical lung carcinoid (TC) is unclear. Aim of this study is to analyze whether synchronous preinvasive multifocal neuroendocrine lesions of the lung with primary TC tumors (MTNET+TC) may represent a negative prognostic factor. A retrospective study, prospectively collected, for TC from two institutional databases was evaluated with a lifelong follow-up from surgery. Patients who did not receive surgery, underwent bronchial resection or lung transplant were excluded. Pathology specimens were all reclassified according the 2015 WHO and the eight AJCC Staging system. Kaplan-Meier(KM) method and Log-rank test reports significance between TC and were MTNET+TC were used. Hence a 1:1 propensity score matching analyses was done by adjusting the imbalance and comparing the overall survival and progression free rate between matched groups with a Cox proportional hazards regression model. A p value of 0.05 or less was considered significant. From January 1983 to December 2013 a total of 234 patients was outlined from the databases (TABLE). A total of 41 patients (17.5%) with MNET+TC were identified. Overall KM progression free survival achieved at 5 and 10 years respectively MNET+TC 93.2% and 83.8% compare to TC 98.4% and 96.1% (p =0.00039). Thirty-six MNET+TC were matched pairs vs. TC alone. Univariate Cox proportional hazards model for matched patients MNET+TC compared to TC was 2.78 (95% CI=0.84-9.3, p=0.095). Difference in progression free rate between matched groups was p<0.001. Synchronous multifocal neuroendocrine preinvasive lesions (MNET) with primary typical carcinoid (TC) lung tumors can be a negative prognostic factor. Careful search of MNET should be always performed in clinical and pathological staging of a suspected primary TC. The increased risk of progression of MNET+TC warrants an accurate and lifelong follow-up.

Bronchial complications requiring intervention have been reported in 9 to 13% of lung transplant (LTx) recipients. We sought to assess the incidence and risk factors of bronchial complications in a large single center cohort.

# 01: Iron deficiency in bariatric surgery patients — a single-centre experience over 5 years {#article-title-2} As the prevalence and severity of obesity have increased in Canada, so too has the demand for bariatric surgery. The objective of this study was to determine the incidence of

Background: As average age and complexity of LTx recipients increase, ECLS as bridge to and recovery from LTx has become prevalent and outcomes are uncertain. Hypothesis: Increased age and exposure to ECLS are associated with more disability captured by the Functional Independence Measure (FIM) from 7 days to 1 year after ICU discharge. Methods: Outcome assessment of 72 LTx recipients (collected concurrently with RECOVER1) was performed at 7 days, 3, 6 and 12 months post ICU discharge. LTx recipients were stratified a priori by age and ECLS status. Results: Four patient groups: (a) ECLS/<50yrs [n=10, median age 31yrs (27-36)]; (b) ECLS/≥ 50yrs [n=7; median age 52yrs (50-61)]; (c) NoECLS/<50yrs [n=11, median age 35yrs (25-41)]; and (d) NoECLS/≥50yrs [(n=44, median age 62yrs (56-66)]. ICULOS (median, IQR) across these groups was: (a) 41 (24-88); (b) 26 (21-31); (c) 18 (11-23); and (d) 23 (17-36). FIM at 7 days after ICU discharge was 18 points lower (p<0.01) in the age group over vs. under 50 yrs and 10 points lower (p=0.05) with exposure to ECLS. From 7 days to 1 year, the rate of improvement in the FIM did not differ across the 4 age/ECLS groups (p=0.71) but at 1 year, those over age 50 yrs had a FIM that was 8 points lower (p=0.03). One-year mortality appeared to vary by ECLS exposure but was not statistically significant: ECLS/<50yrs=30%; ECLS+50yrs=29% and NoECLS/<50yrs=18%; NoECLS+50yrs=15%. Conclusions: Age ≥50 years and any exposure to ECLS among LTx recipients MV for ≥7 days resulted in clinically important reductions in functional independence at 7 days after ICU discharge. 1- Am J Respir Crit Care Med. 2016

Stereotactic body radiation therapy (SBRT) is an option for treatment of patients with non-small cell lung cancer (NSCLC). Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a minimally invasive, diagnostic modality for mediastinal and hilar staging of NSCLC. We evaluated the diagnostic value of EBUS-TBNA in SBRT candidates and compared it to that of computed tomography (CT) and positron emission tomography (PET) scans. Inclusion criteria for this single institutional retrospective study included 1) biopsy-proven or clinically suspicious NSCLC with diameter <6 cm; 2) no evidence of distant metastasis; 3) EBUS-TBNA staging between April 2008 and November 2014; 4) medically SBRT-eligible other than nodal staging. CT and PET positive nodes were defined as short axis ≥1cm and standardized uptake value ≥2.5, respectively. Node positive by clinical-pathologic confirmation (NPCP) was defined as confirmed malignancy by EBUS-TBNA or clinically diagnosed recurrence in hilar or mediastinal lymph nodes within one year after SBRT. The survival after SBRT was compared between CT or PET node-positive but EBUS-TBNA result-negative patients, and a matched cohort (tumor size; radiation dose; operability) who underwent SBRT in our institution within the same time period but without EBUS-TBNA staging. There were 35 eligible patients (mean age 77±8.2, 24 male). Thirty-two (91.4%) patients had pathological confirmation of NSCLC (mean diameter 2.5±1.0 cm) (T1a N=12, T1b N=15, T2a N=7, T2b N=1). Thirty (85.7%) patients were medically inoperable. After EBUS-TBNA, 20 out of 24 patients who had positive nodes in CT (N=13) or PET (N=17) were ultimately pathologically N0. All eleven image-negative patients were N0 following EBUS-TBNA. Thirty-one patients (20 image positive plus 11 image negative) underwent SBRT. Sensitivity/specificity of CT, PET and EBUS-TBNA for NPCP were 42.9/64.3%, 100/64.3% and 57.1/100%, respectively. Positive predictive value of CT and PET for NPCP was 23.1% and 41.2%, respectively. Negative predictive value of CT, PET and EBUS for NPCP was 81.8%, 100% and 90.3%, respectively. A 1:4 (Case; N=20, Control; N=76) match was obtained. Regional failure-free survival (p=0.71, HR=0.88 CI 0.45-1.74) and disease-free survival (p=0.77, HR=1.10 CI 0.58-2.11) of the Case were not significantly different from the ones of Control. There were no major complications related to EBUS procedures. EBUS-TBNA can be considered for invasive staging in SBRT-eligible NSCLC patients with radiographically positive lymph nodes because of its safety and possibility of false positive imaging. If EBUS-TBNA result is negative, these patients may remain candidates for SBRT with comparable outcomes to those who are conventionally selected for SBRT.

The severity of right ventricular failure in patients with high pulmonary arterial pressures is frequently reflected by the development of liver dysfunction, resulting from hepatic congestion. However, little is known about the relationship between preoperative (preop) serum markers of liver dysfunction and prognosis in patients undergoing lung transplantation (LTx) for pulmonary hypertension (PH). Our study aimed to evaluate the role of these markers in the prediction of postoperative (postop) mortality in PH patients undergoing LTx.

The growing demand for suitable lungs for transplantation drives the quest for alternative strategies to expand the donor pool. The aim of this study is to evaluate the outcomes of lung transplantation (LTx) with donation after circulatory determination of death (DCDD) and the impact of selective ex vivo lung perfusion (EVLP). From 2007 to 2013, 673 LTx were performed, with 62 (9.2%) of them using DCDDs (seven bridged cases). Cases bridged with mechanical ventilation/extracorporeal life support were excluded. From 55 DCDDs, 28 (51%) underwent EVLP. Outcomes for LTx using DCDDs and donation after neurological determination of death (DNDD) donors were similar, with 1 and 5-year survivals of 85% and 54% versus 86% and 62%, respectively (p = 0.43). Although comparison of survival curves between DCDD + EVLP versus DCDD-no EVLP showed no significant difference, DCDD + EVLP cases presented shorter hospital stay (median 18 vs. 23 days, p = 0.047) and a trend toward shorter length of mechanical ventilation (2 vs. 3 days, p = 0.059). DCDDs represent a valuable source of lungs for transplantation, providing similar results to DNDDs. EVLP seems an important technique in the armamentarium to safely increase lung utilization from DCDDs; however, further studies are necessary to better define the role of EVLP in this context.

Lymphangioleiomyomatosis (LAM) is a rare disease leading to pulmonary failure. These patients provide unique challenges particularly in the management of the pleural space pre and post LTx. It is not uncommon to be asked whether to perform a pleurodesis in these patients who may come to LTx in the future. We report particularly regarding the relationship between preoperative pleurodesis and perioperative complications. From 01/1990 to 06/2012, of 1262 lung transplants performed in our institution, 15 patients that underwent LTx for LAM were reviewed retrospectively. All patients (n = 15) were women with age at LTx (37 - 59, median: 45). One patient underwent single LTx and the other 14 patients bilateral LTx. (n = 1). With regards to LAM associated preoperative pulmonary complications, there were: chylothoraces (n=3), pneumothoraces (n = 9) and both (n = 2). Ten patients (19 thoracic cavities) had preoperative pleurodesis (5 patients using talc, 1 using doxycycline, 4 using unknown). At the time of LTx, pleural adhesions (mild to severe) were found in 14 thoracic cavities (73.4%). However, intraopetive and postoperative transfusion of red blood cells (RBC) (intrapetive RBC, 3.8 ± 4.4 units in patients with preoperative pleurodesis and 1.4 ± 1.6 without it (p = 0.48) and postoperative RBC, 0.57 ± 0.78 and 1.8 ± 2.1 respectively (p = 0.38)), postoperative incidence of chylothorax (3 patients (30%) in 10 and 1 (25%) in 5 respectively (p = 0.67)), and 30-day mortality (no mortality in both) were not significant between patients with and without preoperative pleurodesis. For all patients, the actual Kaplan-Meier survival was 86.7% at 1 year and 63.2% at 5 years and postoperative lung function was maintained. Pleural symphysis is often required in the management of recurrent pneumothorax and chylous pleural effusions in LAM patients. Preoperative pleurodesis with doxycycline or talc does not appreciably increase rates of complications such as bleeding or chylothorax after LTx for LAM and post LTx lung function and survival rates were excellent.

PurposeAs the population of transplanted patients grows, so does the demand for retransplantation. Lung retransplantation is feasible in select patients, but survival has been inferior compared to initial transplants. Studies of retransplant recipients have generally focused on graft function and survival. Our objective was to perform a detailed analysis of this patient group, including novel variables such as functional status, renal function, HLA antibodies and quality of life.MethodsA retrospective review was performed of patients (n=38) retransplanted in our program between 06/2001 and 08/2013. Variables assessed are outlined in Table 1. We compared best quality of life measurements after the first and second transplants. We used Kaplan-Meier curves with log-rank tests to assess survival and paired t tests for within-patient comparison.ResultsMean age at retransplant was 37y (range 19-60) and median time from first transplant was 54.5 months (0.5-266). Mean preoperative 6MWD was 339m (SD 143). Indications for retransplant were: 36 BOS (94.8), 1 primary graft failure (2.6), 1 recurrent BAC. Median follow up duration was 15.5 months (2-148). Outcomes are detailed in Table 1. DSA post retransplant was present in 12 of 25 (48%) patients with available data. Quality of life scores were similar when compared with initial transplant for either SF-36 (p=0.7) or SGRQ (p=0.9). Survival is shown in Figure 1. Median survival was 4.0 years.ConclusionLung retransplantation is more challenging than first time transplantation. Despite this, our results show that with experience, acceptable clinical, functional and quality of life outcomes are achievable in carefully selected patients.FigView Large Image Figure ViewerDownload Hi-res image Download (PPT) PurposeAs the population of transplanted patients grows, so does the demand for retransplantation. Lung retransplantation is feasible in select patients, but survival has been inferior compared to initial transplants. Studies of retransplant recipients have generally focused on graft function and survival. Our objective was to perform a detailed analysis of this patient group, including novel variables such as functional status, renal function, HLA antibodies and quality of life. As the population of transplanted patients grows, so does the demand for retransplantation. Lung retransplantation is feasible in select patients, but survival has been inferior compared to initial transplants. Studies of retransplant recipients have generally focused on graft function and survival. Our objective was to perform a detailed analysis of this patient group, including novel variables such as functional status, renal function, HLA antibodies and quality of life. MethodsA retrospective review was performed of patients (n=38) retransplanted in our program between 06/2001 and 08/2013. Variables assessed are outlined in Table 1. We compared best quality of life measurements after the first and second transplants. We used Kaplan-Meier curves with log-rank tests to assess survival and paired t tests for within-patient comparison. A retrospective review was performed of patients (n=38) retransplanted in our program between 06/2001 and 08/2013. Variables assessed are outlined in Table 1. We compared best quality of life measurements after the first and second transplants. We used Kaplan-Meier curves with log-rank tests to assess survival and paired t tests for within-patient comparison. ResultsMean age at retransplant was 37y (range 19-60) and median time from first transplant was 54.5 months (0.5-266). Mean preoperative 6MWD was 339m (SD 143). Indications for retransplant were: 36 BOS (94.8), 1 primary graft failure (2.6), 1 recurrent BAC. Median follow up duration was 15.5 months (2-148). Outcomes are detailed in Table 1. DSA post retransplant was present in 12 of 25 (48%) patients with available data. Quality of life scores were similar when compared with initial transplant for either SF-36 (p=0.7) or SGRQ (p=0.9). Survival is shown in Figure 1. Median survival was 4.0 years. Mean age at retransplant was 37y (range 19-60) and median time from first transplant was 54.5 months (0.5-266). Mean preoperative 6MWD was 339m (SD 143). Indications for retransplant were: 36 BOS (94.8), 1 primary graft failure (2.6), 1 recurrent BAC. Median follow up duration was 15.5 months (2-148). Outcomes are detailed in Table 1. DSA post retransplant was present in 12 of 25 (48%) patients with available data. Quality of life scores were similar when compared with initial transplant for either SF-36 (p=0.7) or SGRQ (p=0.9). Survival is shown in Figure 1. Median survival was 4.0 years. ConclusionLung retransplantation is more challenging than first time transplantation. Despite this, our results show that with experience, acceptable clinical, functional and quality of life outcomes are achievable in carefully selected patients. Lung retransplantation is more challenging than first time transplantation. Despite this, our results show that with experience, acceptable clinical, functional and quality of life outcomes are achievable in carefully selected patients.