Trends in the use of hepatitis C viremic donor hearts.

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 < .001), with longer ischemic times (mean: 3.52 hours vs 3.10 hours; P < .001). More than one-half of NAT+ transplantations were performed by 5 individual centers, and a single institution accounted for >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.

Outcomes of Lung Transplantation From Hepatitis C Viremic Donors.

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 Pao2/Fio2 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 < .001). Kaplan-Meier survival analysis demonstrated no difference in survival (P = .56). There were no differences in airway dehiscence (P = .629), acute rejection (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.

Rationale and Design of the Randomized Controlled Trial of New Oral Anticoagulants Versus Warfarin for Post Cardiac Surgery Atrial Fibrillation: The NEW-AF Trial.

OBJECTIVE: 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. BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: The study is ongoing and actively enrolling at the time of the publication. The trial is registered with clinicaltrials.gov under registration number NCT03702582.

Factors Related to Survival in Low-Glomerular Filtration Rate Cohorts Undergoing Lung Transplant.

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.

Impact of Treatment Sequencing on Survival for Patients with Locally Advanced Gastric Cancer.

BACKGROUND: Data are limited concerning the survival outcomes of locally advanced gastric cancer patients according to the multimodality therapy (MMT) administered. METHODS: 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). RESULTS: 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). CONCLUSIONS: 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.

Deregulation of ribosomal protein expression and translation promotes breast cancer metastasis.

Circulating tumor cells (CTCs) are shed into the bloodstream from primary tumors, but only a small subset of these cells generates metastases. We conducted an in vivo genome-wide CRISPR activation screen in CTCs from breast cancer patients to identify genes that promote distant metastasis in mice. Genes coding for ribosomal proteins and regulators of translation were enriched in this screen. Overexpression of RPL15, which encodes a component of the large ribosomal subunit, increased metastatic growth in multiple organs and selectively enhanced translation of other ribosomal proteins and cell cycle regulators. RNA sequencing of freshly isolated CTCs from breast cancer patients revealed a subset with strong ribosome and protein synthesis signatures; these CTCs expressed proliferation and epithelial markers and correlated with poor clinical outcome. Therapies targeting this aggressive subset of CTCs may merit exploration as potential suppressors of metastatic progression.

Impact of Postoperative Complication and Completion of Multimodality Therapy on Survival in Patients Undergoing Gastrectomy for Advanced Gastric Cancer.

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.

Incidence, aetiology and outcomes of major postoperative haemorrhage after pulmonary lobectomy.

OBJECTIVES: Post-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. METHODS: We 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. RESULTS: Following 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 < 0.01) and more likely to have preoperative anaemia (45.2% vs 26.5%; P = 0.01), prior median sternotomy (14.3% vs 6.0%; P = 0.04), an infectious indication (7.1% vs 1.8%; P = 0.01) and operative adhesiolysis (45.2% vs 25.8%; P = 0.01). Compared with non-operative management, reoperation was associated with fewer units of packed red blood cells transfusion (0.4 vs 1.9; P < 0.001), while complication rates were similar and 30-day mortality was absent in either group. CONCLUSIONS: Haemorrhage 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.

Screening high-risk populations for esophageal and gastric cancer.

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.

Morbidity and Mortality of Total Gastrectomy: a Comprehensive Analysis of 90-Day Outcomes.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Outcomes of Extended Lymphadenectomy for Gastroesophageal Carcinoma: A Large Western Series.

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.