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Background Historically, a glomerular filtration rate (GFR) of less than 50 mL/min per 1.73 m2 has been considered a contraindication to lung transplantation. Combined or sequential lung–kidney transplantation is an option for those with a GFR less than 30 mL/min per 1.73 m2. Patients with a GFR of 30 to 50 mL/min per 1.73 m2 are provided with no options for transplantation. This study explores factors associated with improved survival in patients who undergo isolated lung transplantation with a GFR of 30 to 50 mL/min per 1.73 m2. Methods The United Network for Organ Sharing database was queried for adult patients undergoing primary isolated lung transplantation between January 2007 and March 2018. Regression models were used to identify factors associated with improved survival in lung recipients with a preoperative GFR of 30 to 50 mL/min per 1.73 m2. The propensity score method was used to match highly performing patients (outpatient recipients aged less than 60 years) with a GFR of 30 to 50 mL/min per 1.73 m2 with patients who had a GFR greater than 50 mL/min per 1.73 m2. Kaplan-Meier, Cox, and logistic regression analyses compared outcomes in matched populations. Results A total of 21,282 lung transplantations were performed during the study period. Compared with patients with a GFR greater than 50 mL/min per 1.73 m2, survival was significantly worse for patients with a GFR of 30 to 50 mL/min per 1.73 m2. Multivariate analysis of patients with a GFR of 30 to 50 mL/min per 1.73 m2 demonstrated outpatient status and age less than 60 years to be predictive of superior survival. After propensity matching, survival of this highly performing subset with a GFR of 30 to 50 mL/min per 1.73 m2 was no different from that of patients with a normal GFR. Conclusions Outpatient recipients aged less than 60 years represent an optimal subset of patients with a GFR of 30 to 50 mL/min per 1.73 m2. Lung transplant listing should not be declined based only on a GFR less than 50 mL/min per 1.73 m2.

Adequate and durable recovery in patients supported with venoarterial (VA) extracorporeal membrane oxygenation (ECMO) can be challenging to predict. Extracorporeal membrane oxygenation weaning is the process by which the ECMO flows are decreased to assess if a patient is ready for decannulation. The optimal strategies for deciding who to wean and how to wean VA ECMO remain undefined. A retrospective literature review was performed to understand the evidence supporting current practices in ECMO weaning and in particular patient selection and methods. Most published work and expert opinions agree that once the underlying process has resolved, the minimum required physiologic parameters for weaning from ECMO include: hemodynamic stability and cardiac pulsatility, adequate lung function to support oxygenation and ventilation, and evidence of recovered end organ function. Echocardiography is universally used to assess cardiac function during the weaning process. Currently, there is no consensus regarding who is eligible to wean or how to wean ECMO in adults. We have reviewed the literature to summarize the evidence and expert opinions behind VA ECMO weaning, and give an example of the protocol used at our center. We believe this protocol optimizes patient selection for weaning and helps to predict successful decannulation.

Data are limited concerning the survival outcomes of locally advanced gastric cancer patients according to the multimodality therapy (MMT) administered. Single institution, retrospective analysis of 235 patients with locally advanced gastric cancer from 2001 to 2015. All patients met criteria for curative-intent surgery and chemotherapy ± radiation therapy. Treatment regimens were: (1) surgery first with adjuvant chemoradiation therapy (S + Adj); (2) perioperative chemotherapy + surgery (Periop); and (3) total neoadjuvant therapy followed by surgery (TNT + S). One hundred twenty-eight (60.0%) patients received S + Adj, 69 (26.8%) Periop, and 38 (13.2%) TNT + S. Of the 235 patients, 222 (94.5%) received surgery. All intended therapy was received by 81.6% of TNT + S, 44.5% of S + Adj, and 42.0% of Periop patients. MMT was significantly more likely to be completed by TNT + S patients (HR 6.67, p

Adequate and durable recovery in patients supported with venoarterial (VA) extracorporeal membrane oxygenation (ECMO) can be challenging to predict. Extracorporeal membrane oxygenation weaning is the process by which the ECMO flows are decreased to assess if a patient is ready for decannulation. The optimal strategies for deciding who to wean and how to wean VA ECMO remain undefined. A retrospective literature review was performed to understand the evidence supporting current practices in ECMO weaning and in particular patient selection and methods. Most published work and expert opinions agree that once the underlying process has resolved, the minimum required physiologic parameters for weaning from ECMO include: hemodynamic stability and cardiac pulsatility, adequate lung function to support oxygenation and ventilation, and evidence of recovered end organ function. Echocardiography is universally used to assess cardiac function during the weaning process. Currently, there is no consensus regarding who is eligible to wean or how to wean ECMO in adults. We have reviewed the literature to summarize the evidence and expert opinions behind VA ECMO weaning, and give an example of the protocol used at our center. We believe this protocol optimizes patient selection for weaning and helps to predict successful decannulation.

Background The extent of lymph node dissection for patients with gastroesophageal carcinoma remains controversial. We sought to examine the perioperative risk and survival outcomes in a large Western series of patients undergoing limited (D0/D1) vs extended (D1+/D2) lymphadenectomy (LAD) for gastroesophageal carcinoma. Study Design Clinicopathologic and treatment factors for 520 patients with gastroesophageal carcinoma undergoing potentially curative resection at a single institution from 1995 to 2017 were analyzed for their impact on perioperative morbidity and mortality, lymph node yield, and overall survival. Results A total of 362 (70%) patients underwent D0/D1 LAD and 158 (30%) underwent D1+/D2 LAD. Median follow-up was 3.1 years. Patients undergoing D1+/D2 LAD were more likely to have distal tumors, to undergo distal/subtotal/total gastrectomy, and to undergo operation at a more contemporary time than patients undergoing D0/D1 LAD. The median number of lymph nodes examined and the percentage of patients with 16 or more lymph nodes examined was 16 and 53%, respectively, in the D0/D1 group vs 27 and 89%, respectively, in the D1+/D2 group. There were no differences in the rates of major complications (16.6% vs 14.6%) or operative mortality (2.8% vs 0.6%) between the D0/D1 and D1+/D2 groups, respectively. Patients undergoing D1+/D2 LAD had significantly improved overall survival (hazard ratio 0.74; p = 0.035) compared with those undergoing D0/D1 LAD on univariate analysis, but this survival benefit disappeared when controlling for the time period of operation. Conclusions Gastrectomy with extended (D1+/D2) LAD can be performed safely at a high-volume Western center, and it improves nodal yield significantly and ensures accurate pathologic staging.

Background Direct-acting antiviral (DAA) therapy for hepatitis C virus (HCV) has encouraged lung transplantation with HCV positive donors. Early trials have been promising; however, nationwide data have not been previously examined. Methods The United Network for Organ Sharing registry was queried for adult patients receiving lung transplants from 2016 to 2019. We excluded multiorgan transplants, incomplete data, and loss to follow-up. Nucleic acid testing (NAT) determined HCV status. Propensity matching was performed for comparison of outcomes.. Results Hepatitis C virus NAT-positive lungs were transplanted in 189 patients, compared with 9511 recipients of NAT-negative lungs. The HCV NAT-positive donors were younger (mean 33 vs 35 years, P = .017) with higher rates of Pa o 2/Fi o 2 greater than 300 (83.6% vs 76.5%, P = .029). Recipients of NAT-positive lungs had lower lung allocation scores (mean 39.3 vs 42.4, P = .009). Distance traveled was significantly further for HCV viremic donor lungs (mean 416 vs 206 miles, P .999), or reintubation (P = .304). At mean follow-up of 395 days, 63 recipients of NAT-positive lungs (40%) seroconverted, 14 with viremia. One-year mortality rates among seroconverted patients was 6% and did not differ significantly from 14% in nonseroconverted patients or 13.2% in recipients of HCV-negative lungs. Conclusions Short-term outcomes of lung transplantation from HCV viremic donors are promising, with no difference in early complications or survival. The effects of seroconversion and long-term outcomes including chronic rejection and infection need to be further explored.

Objective To examine trends in utilization of hearts from hepatitis C virus (HCV) viremic donors for transplantation, a strategy to expand organ availability. Methods The United Network for Organ Sharing (UNOS) registry was queried for adult patients undergoing heart transplantation between 2015 and 2019. We excluded multiorgan transplants, incomplete data, and loss to follow-up. Nucleic acid testing (NAT) defined HCV status. Results Between 2015 and 2019, a total of 11,393 adults underwent heart transplantation: 326 from HCV NAT+ donors and 11,067 from NAT− donors. The use of NAT+ hearts increased from 1 in 2015 to 137 in 2018 against a static number of NAT− organs. The use of NAT+ hearts varied significantly across regions and individual centers. More than 75% of NAT+ hearts were transplanted in the Northeast region, leading to further travel (mean, 299 miles vs 173 miles for NAT− transplantations; P 20% of all transplantations from viremic donors. Survival in the 2 groups did not differ by Kaplan-Meier analysis (P = .240), and multivariable regression showed no differences in acute rejection (P = .455) or 30-day mortality (P = .490). Of the 326 recipients of NAT+ hearts, 38 seroconverted and 14 became viremic within 1 year. Survival was 100% in the viremic patients and 97.4% in seroconverted patients at 1 year. Conclusions Heart transplantation from HCV viremic donors continues to increase but varies significantly across UNOS regions and individual centers. Short-term outcomes are comparable, but effects of seroconversion and long-term outcomes remain unclear.

This manuscript describes the rationale and design of a randomized, controlled trial comparing outcomes with Warfarin vs Novel Oral Anticoagulant (NOAC) therapy in patients with new onset atrial fibrillation after cardiac surgery.New onset atrial fibrillation commonly occurs after cardiac surgery and is associated with increased rates of stroke and mortality. in nonsurgical patients with atrial fibrillation, NOACs have been shown to confer equivalent benefits for stroke prevention with less bleeding risk and less tedious monitoring requirements compared with Warfarin. However, NOAC use has yet to be adopted widely in cardiac surgery patients.The NEW-AF study has been designed as a pragmatic, prospective, randomized controlled trial that will compare financial, convenience and safety outcomes for patients with new onset atrial fibrillation after cardiac surgery that are treated with NOACs versus Warfarin.Study results may contribute to optimizing the options for stroke prophylaxis in cardiac surgery patients and catalyze more widespread application of NOAC therapy in this patient population.The study is ongoing and actively enrolling at the time of the publication. The trial is registered with clinicaltrials.gov under registration number NCT03702582.

Data are limited concerning the survival outcomes of locally advanced gastric cancer patients according to the multimodality therapy (MMT) administered.Single institution, retrospective analysis of 235 patients with locally advanced gastric cancer from 2001 to 2015. All patients met criteria for curative-intent surgery and chemotherapy ± radiation therapy. Treatment regimens were: (1) surgery first with adjuvant chemoradiation therapy (S + Adj); (2) perioperative chemotherapy + surgery (Periop); and (3) total neoadjuvant therapy followed by surgery (TNT + S).One hundred twenty-eight (60.0%) patients received S + Adj, 69 (26.8%) Periop, and 38 (13.2%) TNT + S. Of the 235 patients, 222 (94.5%) received surgery. All intended therapy was received by 81.6% of TNT + S, 44.5% of S + Adj, and 42.0% of Periop patients. MMT was significantly more likely to be completed by TNT + S patients (HR 6.67, p 0.001). At a median follow-up of 37 months, survival rates on an intention-to-treat basis with TNT + S, Periop, and S + Adj were 52.6%, 59.4%, and 45.3%, respectively. Regimen and completion of MMT significantly affected overall mortality risk. Compared with Periop, TNT + S had similar mortality risk (hazard ratio [HR] 1.28, p = 0.421), whereas S + Adj had increased mortality risk (HR 1.64, p = 0.027).The choice of treatment sequencing has a major impact on completion rates of multimodal therapy in patients with locally advanced gastric cancer. Less than 50% of patients treated with upfront surgery or perioperative chemotherapy receive all intended therapies. TNT has higher intended therapy completion rates and comparable survival compared with perioperative therapy in our data. Further prospective investigations of TNT are warranted.

Purpose This study investigates reasons for rejection of hearts from Hepatitis C+ donors, and predictive factors for acceptance and transplantation. Methods The United Network for Organ Sharing deceased donor registry was queried for adult donors with offers for heart donation from 2015-2020. We excluded patients from whom consent was not obtained or received, and incomplete data. HCV status was determined by nucleic acid testing (NAT). Results A total of 49,045 HCV- and 3,136 HCV+ donors were consented for heart donation from 2015-2020. HCV+ donors were younger (38.5 vs 43.5 years, p Conclusion HCV+ hearts were less likely to be recovered and transplanted despite lower rates of cardiovascular comorbidities. Reasons for discard were primarily unrelated to organ quality or function, and may reflect ongoing skepticism in use of HCV+ organs.

Purpose Hepatitis C (HCV) has become readily treatable in the modern era. The use of HCV+ organs for transplant has shown promising results and increases donor availability. This study is an updated analysis of outcomes after HCV+ heart transplantation in the United States. Methods The United Network for Organ Sharing registry was queried for adult patients who received heart transplants from 2015-2018. Excluded multiorgan transplants, incomplete HCV data, and loss to follow-up. HCV status was classified by serology (Ab+ vs Ab-). Median follow-up was 24 months. Results During the study period, 7529 patients received heart transplants: 136 from HCV Ab+ donors and 7393 from HCV Ab- donors. Seven recipients (5.1%) of HCV Ab+ hearts had HCV+ serology prior to transplant, compared to 129 recipients (1.7%) of HCV Ab- organs (p=0.018). There was no difference in donor age (p=0.489), ejection fraction (p=0.221), gender mismatch (p=0.341), or ABO compatibility (p=0.707). HCV Ab+ transplants involved further travel (mean: 323 vs 149 miles, p Conclusion Transplantation of HCV+ donor hearts has demonstrated promising outcomes thus far, with comparable overall survival and graft outcomes. Ongoing investigation is warranted to observe long-term outcomes.

Background Postoperative complication (POC) adversely impacts long-term survival in patients with gastric cancer, perhaps due in part to lower rates for receipt of multimodality therapy (MMT). We sought to determine the impact of POC on MMT completion rates and overall survival (OS) in patients with locally advanced gastric cancer. Study Design We analyzed 206 patients with locally advanced gastric cancer undergoing curative-intent resection from 2001 to 2015. POCs were graded using Clavien-Dindo classification and survival outcomes were compared between groups. Results One hundred and twenty patients underwent operation followed by chemoradiation therapy, 58 received perioperative chemotherapy, and 28 received total neoadjuvant therapy (TNT). Minor (Clavien-Dindo grade I to II) and major (Clavien-Dindo grade III to IV) POC occurred in 72 (35.0%) and 39 (18.9%) patients, respectively. At median follow-up of 37 months, the 3-year OS of patients experiencing a major, minor, or no POC were 33.3%, 56.9%, and 62.1% (p = 0.023), respectively. In contrast, there was no difference in 3-year OS rates in patients experiencing POC if they completed all intended MMT. Non-TNT patients who experienced a major POC were less likely to complete MMT (hazard ratio 0.36, p = 0.017), and a major POC in these patients had a significant impact on OS (hazard ratio 2.76, p = 0.011), and it did not in patients who completed MMT (hazard ratio 1.58, p = 0.336). Conclusions Major POC adversely affects long-term survival after gastrectomy for gastric cancer, at least in part via lower completion rates of MMT. Treatment strategy designed to ensure the completion of MMT, such as TNT, might be preferable, particularly for patients at high risk for POCs.

OBJECTIVESPost-lobectomy bleeding is uncommon and rarely studied. In this study, we aimed to determine the incidence of post-lobectomy haemorrhage and compare the outcomes of reoperation and non-operative management.METHODSWe conducted a single-institution review of lobectomy cases from 2009 to 2018. The patients were divided into two groups based on the treatment for postoperative bleeding: reoperation or transfusion of packed red blood cells with observation. Transfusion correcting intraoperative blood loss was excluded. One or more criteria defined postoperative bleeding: (i) drop in haematocrit ≥10 or (ii) frank, sustained chest tube bleeding with or without associated hypotension. Covariates included demographics, comorbidities and operative characteristics. Outcomes were operative mortality, complications, length of hospital stay and readmission within 30 days.RESULTSFollowing 1960 lobectomies (92% malignant disease, 8% non-malignant), haemorrhage occurred in 42 cases (2.1%), leading to reoperation in 27 (1.4%), and non-operative management in 15 (0.8%). The median time to reoperation was 17 h. No source of bleeding was identified in 44% of re-explorations. Patients with postoperative haemorrhage were more often male (64.3% vs 41.2%; P CONCLUSIONSHaemorrhage after lobectomy is associated with multiple risk factors. Reoperation may avoid transfusion. A prospective study should optimize timing and selection of operative and non-operative management.

Cancers of the esophagus and stomach remain important causes of mortality worldwide, in large part because they are most often diagnosed at advanced stages. Thus, it is imperative that we identify and treat these cancers in earlier stages. Due to significant heterogeneity in incidence and risk factors for these cancers, it has been challenging to develop standardized screening recommendations. This review summarizes the current recommendations for screening populations at high risk of developing esophagogastric cancers.

Metastasis: A matter of translation? Solid tumors shed a small number of cancer cells into the bloodstream, some of which are believed to contribute to metastasis. The molecular features that confer these circulating tumor cells (CTCs) with metastatic potential are poorly understood. Ebright et al. studied CTCs from breast cancer patients and found that cells with increased expression levels of certain ribosomal proteins and regulators of translation had greater metastatic capacity in a mouse model (see the Perspective by Ma and Jeffrey). Consistent with this finding, patients with higher levels of this subset of CTCs tended to have a poorer prognosis. Science , this issue p. 1468 ; see also p. 1424

Purpose On October 18 2018, UNOS implemented changes to its heart allocation policy which prioritized patients on extracorporeal membrane oxygenation (ECMO) and deprioritized patients with dischargeable left ventricular assist devices (LVADs). We hypothesized that this change may result in worse post-transplant outcomes, since hearts may be given to sicker patients with a lower probability of overall survival. Methods The UNOS database was queried for all adult heart transplants performed between April 2018 and March 2019. The cohort was split into two equal time periods centered on the October 18 2018 policy change. Patient characteristics and outcomes during these two eras were compared to examine the effect of the new allocation system on short term outcomes. Results There were 1,354 heart transplants performed under the old allocation system and 1,186 transplants under the new allocation system. The use of ECMO (52 (4.4%) vs. 15 (1.1%) p Conclusion The new heart allocation policy has significantly altered the management strategy of patients awaiting transplantation, as more patients are bridged with ECMO and TCS-VADs. However, this has not translated into increased short-term mortality after heart transplant. Further studies are necessary to evaluate if this relationship persists after longer follow up.

Purpose Kidney failure after lung transplantation is associated with worse outcomes. In clinical practice, precautions are taken in patients with preoperative kidney disease to minimize the risk of post-transplant renal failure. A subset of patients with normal pre-operative kidney function require renal replacement therapy (RRT) after transplant and may benefit from similar precautions. Methods The Scientific Registry for Transplant Recipients (SRTR) database was queried for all adult, primary, lung only transplantations performed between 05/2005 and 03/2019. Patients with normal pre-transplant glomerular filtration rate (I.e. GFR >= 90mL/min/1.73 m2) were included in the analysis. Multivariable logistic regression identified factors associated with post-transplant RRT. Results 14, 101 adult lung recipients with normal GFR were included in the analysis. 812 patients (5.76%) required RRT post-transplantation. Patients who required RRT had higher lung allocation scores (47.1 vs. 40.9, p Conclusion Post-transplant renal failure is associated with significantly worse survival in lung recipients. In patients with normal pre-operative renal function, particular precautions should be taken to prevent renal decline in those undergoing bilateral lung transplantation, who have diabetes mellitus and who are in the ICU at the time of transplantation.

Purpose Current ice bag heart preservation technique is associated with wide fluctuations of organ temperature, resulting in sub-optimal preservation and freeze injury. These shortcomings may be particularly impactful with increased ischemic times given increasing retrieval distances associated with new organ allocation. In comparison, the SherpaPakTM Cardiac Transport System is designed for the static hypothermic preservation of donor hearts within a controlled temperature range. This method avoids excess cooling and optimizes preservation during transportation. The purpose of this study is to assess the outcomes of heart transplantation using the static hypothermic preservation (SHP) system as compared with conventional ice bag preservation (IP). Methods Retrospective cohort analysis was performed on adult patients undergoing heart transplantation between 6/30/2018 and 09/02/2019 at a single institution. Donor and recipient baseline characteristics and post-transplant outcomes were compared between patients receiving organs with SHP versus IP for donor heart transport. Patients who underwent multiple organ transplantation were excluded. Results Of 48 consecutive patients undergoing heart transplantation, 20 (41.7%) organs were transported using SHP and 28 (58.3%) using IP. SHP was used for older recipients (61.5 vs 57.5 years, p=0.02), and longer donor heart cold ischemic times (4.35 vs 3.49 hours, Figure1, p=0.018). There were no 30-day mortalities. Despite longer ischemic times, there was no difference in the incidence of any primary graft dysfunction (PGD) (14.3% vs 15.0%, p=1) or severe PGD requiring extracorporeal membrane oxygenation (10.7% vs 5.0%, Table1, p=0.63) between SHP and IP. Conclusion There was no worsening in clinical outcomes with SHP despite longer ischemic times and older recipient ages. With new heart allocation changes, SHP may be beneficial in cases with further transport distances, by mitigating the effect of prolonged ischemic times.

Total gastrectomy (TG) is a complex procedure that carries a high risk of morbidity and mortality and in which patients may experience post-operative sequelae well past the standard 30-day follow-up period. Large studies from high-volume centers with detailed 90-day follow-up data are needed to provide benchmarks for high-quality care for this complex procedure. Single-institution, retrospective review of a comprehensive gastric cancer database of 148 patients undergoing curative intent TG from 2000 to 2017. Clinicopathologic and treatment factors were analyzed for their impact on 90-day outcomes. The median age of the cohort was 66 years, and 61% were male. Neoadjuvant chemotherapy and radiation therapy were delivered to 32% and 11% of patients, respectively. Open and laparoscopic TG were performed in 93% (n = 137) and 7% (n = 11) of patients, respectively. Extended lymphadenectomy, pancreatectomy, and splenectomy were performed in 37%, 4.7%, and 19% of patients, respectively. The 30- and 90-day mortality rates were 2.0% and 3.4%, respectively. At least one 90-day complication was experienced by 43.9% (n = 65) of patients, and 14% (n = 21) experienced a Clavien–Dindo grade 3 or 4 complication. Anastomotic leak occurred in 5.4% (n = 8) of patients, half of which required an invasive intervention. Median length of stay was 8 days. The readmission rate was 22%, and most readmissions were due to dehydration and/or nutritional compromise. This study defines 30- and 90-day post-operative outcomes after total gastrectomy in a high-volume center. These outcomes data are critical to the improvement of the informed consent process and as benchmarks for future quality improvement initiatives.