Evaluation of association between center colorectal neuroendocrine neoplasm volume and survival among patients with colorectal neuroendocrine carcinoma.

BACKGROUND: Although correlation between center volume and survival has been reported for several complex cancers, it remains unknown if this is true for colorectal neuroendocrine carcinomas (CRNECs). We hypothesized that higher center annual volume of colorectal neuroendocrine neoplasm resections would be associated with overall survival (OS) for patients with CRNECs. METHODS: Patients in the National Cancer Database diagnosed with stages I-III CRNEC between 2006 and 2018 and who underwent surgical resection were identified. The mean annual colorectal neuroendocrine neoplasm resection volume threshold associated with significantly worse mortality hazard was determined using restricted cubic splines. Kaplan-Meier (KM) method was used to compare OS, while Cox proportional hazards model was used for multivariable analysis. RESULTS: There were 694 patients with CRNEC who met inclusion criteria across 1229 centers. Based on the cubic spline, centers treating fewer than one colorectal neuroendocrine neoplasm patient every 3 years on average had worse outcomes. Centers below this threshold were classified as low-volume (LV) centers corresponding with 42% of centers and about 15% of the patient cohort. In unadjusted survival analysis, LV patients had a median OS of 14 months (95% confidence interval [CI]: 10-19) while those treated at HV centers had a median OS of 33 months (95% CI: 25-49). In multivariable analysis, resection at a LV center was associated with increased risk of mortality (1.42 [95% CI: 1.01-2.00], p = 0.04). CONCLUSION: CRNEC patients have a dire prognosis; however, treatment at an HV center may be associated with decreased risk of mortality.

Epidemiology and survival outcomes of colorectal mixed neuroendocrine-non-neuroendocrine neoplasms and neuroendocrine carcinoma.

BACKGROUND: Mixed neuroendocrine-non-neuroendocrine neoplasms are a rare subtype of neuroendocrine neoplasm consisting of ≥30% each of neuroendocrine and non-neuroendocrine differentiation. Neuroendocrine carcinomas are poorly differentiated neuroendocrine tumors. The epidemiology and prognosis of colorectal mixed neuroendocrine-non-neuroendocrine neoplasms and neuroendocrine carcinomas are not clearly defined in the literature. We sought to examine the presentation, patterns of care, and outcomes of patients with mixed neuroendocrine-non-neuroendocrine neoplasms and neuroendocrine carcinomas. METHODS: We identified patients diagnosed with stage I-III colorectal (excluding appendix) mixed neuroendocrine-non-neuroendocrine neoplasms or neuroendocrine carcinomas with only one-lifetime cancer diagnosis who underwent surgical resection between 2010 and 2018 from the National Cancer Database. We performed bidirectional selection to identify variables to include in a multivariable Cox proportional hazards model. RESULTS: We identified 189 patients with a diagnosis of stage I to III colorectal mixed neuroendocrine-non-neuroendocrine neoplasms, 66% of whom had poorly differentiated tumors and 482 with neuroendocrine carcinomas. Among patients with stage III disease, 68% of patients with mixed neuroendocrine-non-neuroendocrine neoplasms and 54% of patients with neuroendocrine carcinomas received adjuvant chemotherapy. The median survival for the overall patients with mixed neuroendocrine-non-neuroendocrine neoplasms and neuroendocrine carcinomas cohorts were 38 and 42 months, respectively (P = .22), and the median survival for patients with mixed neuroendocrine-non-neuroendocrine neoplasms and neuroendocrine carcinomas with stage III disease were 30 and 25 months, respectively (P = .27). In multivariable analysis, fewer number of positive nodes and receipt of adjuvant chemotherapy were independently associated with decreased risk of mortality for patients with mixed neuroendocrine-non-neuroendocrine neoplasms and neuroendocrine carcinomas. CONCLUSION: Adjuvant chemotherapy is associated with improved survival in stage III mixed neuroendocrine-non-neuroendocrine neoplasms and neuroendocrine carcinomas. Future studies are warranted to identify subsets of patients benefiting most from adjuvant therapy.

Krt14 and Krt15 differentially regulate regenerative properties and differentiation potential of airway basal cells.

Keratin expression dynamically changes in airway basal cells (BCs) after acute and chronic injury, yet the functional consequences of these changes on BC behavior remain unknown. In bronchiolitis obliterans (BO) after lung transplantation, BC clonogenicity declines, which is associated with a switch from keratin15 (Krt15) to keratin14 (Krt14). We investigated these keratins' roles using Crispr-KO in vitro and in vivo and found that Krt14-KO and Krt15-KO produce contrasting phenotypes in terms of differentiation and clonogenicity. Primary mouse Krt14-KO BCs did not differentiate into club and ciliated cells but had enhanced clonogenicity. By contrast, Krt15-KO did not alter BC differentiation but impaired clonogenicity in vitro and reduced the number of label-retaining BCs in vivo after injury. Krt14, but not Krt15, bound the tumor suppressor stratifin (Sfn). Disruption of Krt14, but not of Krt15, reduced Sfn protein abundance and increased expression of the oncogene dNp63a during BC differentiation, whereas dNp63a levels were reduced in Krt15-KO BCs. Overall, the phenotype of Krt15-KO BCs contrasts with Krt14-KO phenotype and resembles the phenotype in BO with decreased clonogenicity, increased Krt14, and decreased dNp63a expression. This work demonstrates that Krt14 and Krt15 functionally regulate BC behavior, which is relevant in chronic disease states like BO.

A Matched Survival Analysis of Lung Transplant Recipients With Coronavirus Disease 2019-Related Respiratory Failure.

BACKGROUND: Lung transplantation is an acceptable and potentially life-saving treatment option for coronavirus disease 2019 (COVID-19)-induced acute respiratory distress syndrome and pulmonary fibrosis. This study was conducted to determine whether recipients of lung transplantation (LT) for COVID-19-related lung disease have comparable outcomes to other recipients with a similar level of lung dysfunction. METHODS: The Organ Procurement and Transplant Network database was queried for adult LT candidates between 2006 and 2021. Recipients with COVID-19-related respiratory failure were matched 1:2 using a nearest-neighbor algorithm. Kaplan-Meier methods with log-rank tests were used to compare long-term survival. A proportional hazards model was used to calculate risk of death. RESULTS: A total of 37,333 LT candidates from all causes were compared with 334 candidates from COVID-19-related respiratory failure. COVID-19 recipients were more likely to be younger (50 vs 57 years, P < .001), male (79% vs 60%, P < .001), require extracorporeal membrane oxygenation (56.3% vs 4.0%, P < .001), and have worse lung function (lung allocation score, 82.4 vs 47.8; P < .001) at transplantation. Subsequently, 227 COVID-19 recipients were matched with 454 controls. Patients who received a transplant for COVID-19 had similar rates of mechanical ventilation, extracorporeal membrane oxygenation, postoperative complications, and functional status at discharge compared with controls. There was no difference in overall survival or risk of death from COVID-19 (hazard ratio, 0.82; 95% CI, 0.45-1.53; P = .54). CONCLUSIONS: Six-month survival for recipients of LT for COVID-19-related respiratory failure was comparable to that of other LT recipients.

The "Classification Pendulum" of Stage I Colorectal Cancer: A National Level Analysis of the Survival Difference Between T1 and T2 Colorectal Cancer.

BACKGROUND: The eighth edition of the American Joint Committee on Cancer classifies nonmetastatic, node-negative colorectal cancers invading the submucosa (T1) and muscularis propria (T2) as stage I tumors without additional subclassification. OBJECTIVE: The aim of the study was to compare survival of T1N0M0 versus T2N0M0 colorectal cancers and to investigate factors associated with decreased survival. DESIGN: This was an analysis of 2 large population-based data sets. SETTINGS: The study was conducted analyzing data from the Surveillance Epidemiology and End Result program and the National Cancer Database. PATIENTS: Adult patients undergoing major resection without additional therapy for stage I colorectal cancer were included. MAIN OUTCOME MEASURES: Overall and disease-specific survival for T1 versus T2 cancers were measured. Subgroup analyses by tumor location (colon versus rectum) were performed. RESULTS: A total of 30,228 (36.4% T1 and 63.6% T2) and 41,670 (41.1% T1 and 58.9% T2) patients were identified in the Surveillance Epidemiology and End Result database and the National Cancer Database. The 5-year overall survival rates were 87.1% and 86.2% for patients with T1 versus 82.7% and 80.7% for patients with T2 (p < 0.001) in the Surveillance Epidemiology and End Result database and the National Cancer Database. The 10-year overall survival rates were 71.3% and 66.3% for patients with T1 versus 62.2% and 57.2% for patients with T2 tumors (p < 0.001) in the Surveillance Epidemiology and End Result database and the National Cancer Database. The 5- and 10-year disease-specific survival for colorectal cancer in the Surveillance Epidemiology and End Result database was 97.0% (T1) versus 95.2% (T2) and 94.1% (T1) versus 90.3% (T2). Black race (HR = 1.26 and 1.65 for overall survival and disease-specific survival in the Surveillance Epidemiology and End Result database; HR = 1.20 for overall survival in the National Cancer Database) was associated with worse survival. LIMITATIONS: The study was limited by intrinsic biases related to large administrative data sets. CONCLUSIONS: Within stage I colorectal cancer, T2 tumors have decreased overall survival and disease-specific survival as compared with T1 cancers. This survival difference may justify revising the American Joint Committee on Cancer staging system to include the subclassification of stage Ia (T1N0M0) and stage Ib (T2N0M0). See Video Abstract at http://links.lww.com/DCR/B659. LA CLASIFICACIN PNDULO PARA EL CNCER COLORRECTAL EN ESTADIO I UN ANLISIS A NIVEL NACIONAL DE LA DIFERENCIA DE SOBREVIDA ENTRE EL CNCER COLORRECTAL T Y T: ANTECEDENTES:La octava edición del American Joint Committee on Cancer, clasifica los cánceres colorrectales no metastásicos con ganglios negativos, que invaden la submucosa (T1) y la muscularis propia (T2) como tumores en estadio I sin subclasificación adicional.OBJETIVO:El objetivo del estudio fue comparar la sobrevida de los cánceres colorrectales T1N0M0 versus T2N0M0 e investigar los factores asociados con la disminución de la sobrevida.DISEÑO:Análisis de dos grandes conjuntos de datos poblacionales.MARCO:El estudio se realizó analizando datos del Programa de Epidemiología de Vigilancia y Resultados Finales (SEER) y la Base de Datos Nacional del Cáncer.PACIENTES:Pacientes adultos en los cuales se realizó una resección mayor sin terapia adicional por cáncer colorrectal en estadio I.PRINCIPALES VARIABLES ANALIZADAS:Sobrevida global y específica de la enfermedad para los cánceres T1 versus T2. Se realizó un análisis de subgrupos según la ubicación del tumor (colon versus recto).RESULTADOS:Se incluyeron un total de 30.228 (36,4% T1 y 63,6% T2) y 41.670 (41,1% T1 y 58,9% T2) pacientes en las bases de datos SEER y la Base de Datos Nacional del Cáncer, respectivamente. La sobrevida global a 5 años fue del 87,1% y el 86,2% para los pacientes con T1 frente al 82,7% y el 80,7% de los pacientes con T2 (p < 0,001) en el SEER y la Base de Datos Nacional del Cáncer, respectivamente. La sobrevida global a 10 años fue del 71,3% y el 66,3% para los pacientes con T1 frente al 62,2% y el 57,2% de los pacientes con tumores T2 (p < 0,001) en el SEER y la Base de Datos Nacional del Cáncer, respectivamente. La sobrevida específica de la enfermedad a 5 y 10 años para el cáncer colorrectal en el SEER fue del 97,0% (T1) frente al 95,2% (T2) y del 94,1% (T1) frente al 90,3% (T2), respectivamente. La grupo étnico afroamericano se asoció con una sobrevida menor (Hazard Ratio -HR 1,26 y 1,65 para la sobrevida general y sobrevida específica de la enfermedad-SEER; HR 1,20 para la sobrevida general-Base de de Datos Nacional del Cáncer).LIMITACIONES:Sesgos intrínsecos relacionados con el análisis de grandes conjuntos de datos.CONCLUSIONES:Dentro del cáncer colorrectal en estadio I, los tumores T2 han disminuido la sobrevida general y la sobrevida específica de la enfermedad, en comparación con los cánceres T1. Esta diferencia de sobrevida puede justificar la revisión del sistema de estadificación del American Joint Committee on Cancer para incluir la subclasificación del estadio Ia (T1N0M0) y el estadio Ib (T2N0M0). Consulte Video Resumen en http://links.lww.com/DCR/B659.

Does Fragmentation of Care in Locally Advanced Rectal Cancer Increase Patient Mortality?

OBJECTIVE: To evaluate health care fragmentation in patients with stage II and III rectal cancers. BACKGROUND: Fragmentation of care among multiple hospitals may worsen outcomes for cancer patients. METHODS: National Cancer Database was queried for adult patients who underwent radiation and surgery for locally advanced (stage II-III) rectal adenocarcinoma from 2006 to 2015. Fragmented care was defined as receiving radiation at a different hospital from surgery. Descriptive statistics characterized patients, and survival probability was plotted using the Kaplan-Meier method and a Cox proportional hazards model. RESULTS: A total of 37,081 patients underwent surgery and radiation for stage II-III rectal cancer from 2006 to 2015 (24,102 integrated care vs. 12,979 fragmented care). Patients who received fragmented care (hazard ratio [HR] 1.105; 95% CI 1.045-1.169) had a higher risk of mortality. Patients who received at least surgery (HR 0.84; 95% CI 0.77-0.92) at academic hospitals had a lower risk of mortality. Academic hospitals had a higher proportion of patients with fragmented care (38.0 vs. comprehensive community 32.8% vs. community 33.8%, p < 0.001). Within academic hospitals, fragmented care portended worse survival (integrated academic 80.0% vs. fragmented academic 76.7%, p = 0.0002). Fragmented care at academic hospitals had increased survival over integrated care at community hospitals (fragmented academic 76.7 vs. integrated community 72.2%, p = 0.00039). CONCLUSIONS: In patients with stage II-III rectal cancer, patients who have integrated care at academic hospitals or at least surgery at academic centers had better survival. All efforts should be made to reduce care fragmentation and surgery at academic centers should be prioritized.

Impact of minimally invasive gastrectomy on use of and time to adjuvant chemotherapy for gastric adenocarcinoma.

BACKGROUND: Chemotherapy improves outcomes in patients with resectable gastric cancer. Minimally invasive gastrectomy (MIS) rates are increasing, though the impact of MIS on postoperative chemotherapy remains uncertain. This study examines the impact of MIS vs open gastrectomy (OG) on utilization of adjuvant chemotherapy for high-risk gastric cancer. METHODS: Patients in the National Cancer Database who underwent resection for high-risk gastric adenocarcinoma between 2010 and 2015 were included. Patients were stratified by surgical approach (MIS vs OG) and analyzed using multivariable regression modeling. Primary endpoints were utilization of and time to initiation of adjuvant chemotherapy. RESULTS: Overall, 23 071 patients were included; 16 595 (71.9%) underwent OG and 6476 (28.1%) underwent MIS. After adjusting for patient and tumor characteristics, MIS was not associated with increased use of adjuvant chemotherapy (odds ratio [OR]: 1.027, 95% confidence interval [CI]: 0.95 to 1.11, P = .50), and time to initiation of chemotherapy was similar (-2% change, 95% CI: -5% to +1%, P = .27). MIS was associated with shorter hospital stays (-1 day). Thirty-day readmission rates, 90-day mortality, and overall survival were similar between groups. CONCLUSIONS: In this study, while MIS for gastric adenocarcinoma was associated with shorter hospital stays and comparable survival, it was not associated with improved utilization or time to initiation of adjuvant chemotherapy.

Pretransplant Desensitization with Costimulation Blockade and Proteasome Inhibitor Reduces DSA and Delays Antibody-Mediated Rejection in Highly Sensitized Nonhuman Primate Kidney Transplant Recipients.

BACKGROUND: Patients with broad HLA sensitization have poor access to donor organs, high mortality while waiting for kidney transplant, and inferior graft survival. Although desensitization strategies permit transplantation via lowering of donor-specific antibodies, the B cell-response axis from germinal center activation to plasma cell differentiation remains intact. METHODS: To investigate targeting the germinal center response and plasma cells as a desensitization strategy, we sensitized maximally MHC-mismatched rhesus pairs with two sequential skin transplants. We administered a proteasome inhibitor (carfilzomib) and costimulation blockade agent (belatacept) to six animals weekly for 1 month; four controls received no treatment. We analyzed blood, lymph node, bone marrow cells, and serum before desensitization, after desensitization, and after kidney transplantation. RESULTS: The group receiving carfilzomib and belatacept exhibited significantly reduced levels of donor-specific antibodies (P=0.05) and bone marrow plasma cells (P=0.02) compared with controls, with a trend toward reduced lymph node T follicular helper cells (P=0.06). Compared with controls, carfilzomib- and belatacept-treated animals had significantly prolonged graft survival (P=0.02), and renal biopsy at 1 month showed significantly reduced antibody-mediated rejection scores (P=0.02). However, four of five animals with long-term graft survival showed gradual rebound of donor-specific antibodies and antibody-mediated rejection. CONCLUSIONS: Desensitization using proteasome inhibition and costimulation blockade reduces bone marrow plasma cells, disorganizes germinal center responses, reduces donor-specific antibody levels, and prolongs allograft survival in highly sensitized nonhuman primates. Most animals experienced antibody-mediated rejection with humoral-response rebound, suggesting desensitization must be maintained after transplantation using ongoing suppression of the B cell response.

Carotid stenting and endarterectomy and contralateral carotid occlusion.

BACKGROUND: The presence of contralateral carotid occlusion (CCO) has been controversial throughout the history of carotid intervention. Some studies cite a higher stroke risk in the setting of CCO, whereas other studies document no difference in stroke risk. We investigated the risk of stroke after intervention in the setting of CCO in a large, national, validated dataset. METHODS: Data were obtained from the 2011-2014 American College of Surgeons National Surgical Quality Initiative Project files using targeted carotid endarterectomy (CEA), carotid angioplasty, and carotid artery stenting (CAS) data. Patient and procedural characteristics, and 30-day postoperative outcomes were compared using Pearson χ2 tests for categorical variables and Wilcoxon rank-sum tests for continuous variables. Logistic regression was used for multivariable analysis. The primary outcome measure was the stroke rate, with a secondary outcome of major adverse cardiovascular events. RESULTS: During the study period, 11,948 CEA and 422 CAS procedures were available for study, with significantly fewer CEA (4.73% of all CEA) than CAS (9.95%; P < .0001) occurring in the setting of CCO. CAS was associated with more severe degree of stenosis than CEA (P = .045). Multivariable logistic regression showed that stroke after procedures was higher in patients with CCO than without CCO (odds ratio, 1.73; 95% confidence interval, 1.08-2.76; P = .02), but specific procedure (CEA vs CAS) was not associated with stroke while controlling for confounders. However, when evaluating our secondary composite outcome, CCO was not associated with the outcome while controlling for confounders. CONCLUSIONS: There is currently a bias that CCO confers a higher risk on patients undergoing carotid procedures and this notion is manifest in the proportion of CEA and CAS procedures done in the setting of CCO. Our study observes that CCO provides only a minor influence on periprocedural stroke risk and that other factors are more closely tied to outcomes of CEA and CAS.

Health Career Academy: Addition of a Surgical Case-Based Learning Curriculum Captures the Interest of High School Students.

OBJECTIVE: The Health Career Academy (HCA) is a national program which provides a structure to introduce underserved high school students to healthcare careers. Utilizing the HCA framework, we adapted the curriculum to emphasize surgical cases and invited physicians to enrich the learning experience. DESIGN, SETTING, AND PARTICIPANTS: Medical students adapted a surgical case-based learning (CBL) curriculum at a local high school serving students from a primarily ethnic minority and low-income community (61% Black, 20% Hispanic; 58% free or reduced lunch). Each grade level received a minimum of ten, 90-minute CBL sessions. Expert faculty lecturers supplemented lessons. Medical student volunteers and 10th and 11th grade students completed postsemester surveys. RESULTS: Over four semesters, HCA held 44 sessions, with 81 students graduating from the program. A total of 66% of sessions featured at least one faculty volunteer. A total of 36 students in 10th and 11th grade and 15 medical student volunteers completed postparticipation surveys. A total of 46.2% of 11th grade students previously participated in the 10th grade curriculum. On a scale of 1 to 4, students rated HCA highly in its overview of career options (mean 3.61, [SD 0.5]) and instilling understanding of patient care (3.78 [0.42]). Students enjoyed learning about career paths (3.61 [0.50]) and health topics (3.83 [0.39]). Of 10th and 11th grade students, 100% considered a healthcare career, with 34.8% of 10th and 61.5% of 11th grade students expressing interest in pursuing a surgical specialty. After volunteering, medical students felt like better educators (4.47 [0.64]) and were more likely to pursue teaching roles (4.2 [0.86]). CONCLUSIONS: The Duke HCA chapter implemented the HCA program featuring CBL sessions emphasizing surgical cases. This program engaged minority students and potentially contributed to student interest in surgical careers. It helped to prepare medical students for future teaching roles. An interactive, surgery-focused program may increase the number of minority youth interested in pursuing health careers.

Underutilization of surgical resection in patients with pancreatic acinar cell carcinoma.

BACKGROUND: Pancreatic acinar cell carcinoma (pACC) is a rare malignancy and surgical utilization has been historically low in these patients. Contemporary outcomes for this patient population remain unknown. METHODS: The 1998-2012 National Cancer Data Base was queried for baseline characteristics in patients with pACC. Patients with potentially operable disease (stage I/II) were grouped by surgical resection. Multivariable logistic regression was used to predict factors associated with resection. Survival was estimated using Kaplan-Meier analysis. A proportional hazards model identified factors associated with overall survival. RESULTS: 980 patients were identified. Mean age at diagnosis was 64 years. Tumors were more common in men (68%), white patients (88%), and within the pancreatic head (57%). Thirty-four percent of patients with localized disease failed to undergo resection. Five-year survival was higher among patients who underwent resection (42% vs. 9%, p < 0.001). In patients with resectable disease, male sex, older age, black race, tumors within the pancreatic head, lower grade tumors and treatment at non-academic centers are associated with failure to undergo surgery. CONCLUSION: Patients with localized pACC have increased survival after resection. However, in this contemporary analysis, resection continues to be underutilized and new efforts to increase resection rates should be undertaken.

Primary sarcomas of the pancreas: A review of 253 patients from the National Cancer Data Base.

INTRODUCTION: Primary sarcomas of the pancreas are rare, and the limited data regarding their presentation, oncologic profile, and survival have been derived from small case series. METHODS: The National Cancer Data Base (1998-2012) was queried for patients with primary sarcomas of the pancreas. Demographic and clinical features at the time of diagnosis were evaluated for all patients. Subjects who underwent surgical resection were identified, and logistic regression was used to identify variables associated with resection. A Cox proportional hazards model was developed to identify factors associated with survival. RESULTS: In total, 253 patients were identified. The mean age at diagnosis was 63 years, with tumors occurring more frequently in women (57.3%) and those of white race (79.8%). Tumors in the head of the pancreas were most common (63.3%). The mean size was 7.5 cm. Only 100 patients (39.5%) underwent resection, with younger age (OR = 0.763, p = 0.04) and smaller tumor size (OR = 0.978, p < 0.01) associated with resection. Chemotherapy and radiation therapy use were similar in patients who underwent resection and those who did not. Patients who underwent resection had a median survival of 17 months, compared to 6 months for patients who were not resected (p < 0.01). Following adjustment, only older age (HR 1.257, p = 0.03) and higher tumor grade (HR 1.997, p = 0.01) were associated with an increased risk of death in resected patients. CONCLUSIONS: Primary pancreatic sarcomas are rare and the majority of patients do not undergo resection; thus, little is known about their oncologic profile or outcomes following pancreatectomy. Patients who undergo resection have markedly improved survival; older age and higher tumor grade are associated with decreased survival.

Local excision results in comparable survival to radical resection for early-stage rectal carcinoid.

BACKGROUND: Controversy exists regarding current National Comprehensive Cancer Network guidelines, which recommend local excision for rectal carcinoids ≤2 cm and radical resection for tumors >2 cm. Given the limited data examining optimal surgical approach for these lesions, we queried a national database to determine the impact of extent of resection on survival. METHODS: Patients undergoing treatment for clinical stage I and II rectal carcinoid (RC) were identified from the National Cancer Data Base (1998-2012). The association between extent of surgery, tumor size, and the likelihood of pathologic lymph node positivity was examined. Kaplan-Meier analysis was used to compare overall survival. RESULTS: In total, 1900 patients were identified, of whom 1644 (86.5%) were treated with local excision, and 256 (13.5%) were treated with radical resection. A significant majority of patients with tumors ≤2.0 cm (89.0%) and nearly half with tumors 2.1-4.0 cm (44.8%) or >4.0 cm (45.8%) underwent local excision. Nodal positivity was correlated with tumor size (7.1% positivity with ≤2.0 cm tumors, 31.3% with 2.1-4.0 cm tumors, and 50.0% with >4 cm tumors). However, 5-y survival was equivalent between surgical approaches for tumors ≤2 cm (93.0% versus 93.0%) and tumors 2.1-4.0 cm (76.0% versus 76.0%). CONCLUSIONS: We demonstrate in early-stage RC that nearly half of intermediate and large tumors are being treated with local excision outside National Comprehensive Cancer Network guidelines. In addition, radical resection does not appear to be associated with improved overall survival for tumors of any size. These findings suggest that the preferred approach to early-stage RCs without aggressive biological characteristics is local excision due to the decreased morbidity and mortality versus radical resection.

Contemporary Strategies and Barriers to Transplantation Tolerance.

The purpose of this review is to discuss immunologic tolerance as it applies to solid organ transplantation and to identify barriers that hinder the achievement of this long-term goal. First, the definition of tolerance and an introduction of mechanisms by which tolerance exists or can be achieved will be discussed. Next, a review of contemporary attempts at achieving transplant tolerance will be described. Finally, a discussion of the humoral barriers to transplantation tolerance and potential ways to overcome these barriers will be presented.

Single-Center Long-Term Analysis of Combined Liver-Lung Transplant Outcomes.

BACKGROUND: Combined lung-liver transplantation (LLT) applies 2 technically challenging transplants in 1 patient with severe 2-organ failure. METHODS: Institutional medical records and United Network for Organ Sharing database were queried for patients at our institution that underwent LLT from 2000 to 2016. RESULTS: Twelve LLTs were performed from 2000 to 2016 including 9 male and 3 female recipients with a median age of 28.36 years. Indications for lung transplantation were cystic fibrosis (8), idiopathic pulmonary fibrosis (3), and pulmonary fibrosis secondary to hepatopulmonary syndrome (1). Indications for liver transplantation were cystic fibrosis (8), alcoholic cirrhosis (1), idiopathic cirrhosis (2), and alpha-1 antitrypsin deficiency (1). Median forced expiratory volume in 1 second at transplant was 27.8% (±20.38%), and mean Model for End-Stage Liver Disease was 10.5 (±4.68). Median hospital stay was 44.5 days. Seventy-five percent of recipients had 1+ new infection during their transplant hospitalization. Patients experienced 0.68 incidences of acute rejection per year with a 41.7% (95% confidence interval, 21.3%-81.4%) probability of freedom from rejection in the first-year. Patient survival was 100% at 30 days, 91.6% at 1 year, and 71.3% at 3 years. At the time of analysis, 7 of 12 patients were alive, of whom 3 survived over 8 years post-LLT. Causes of death were primary liver graft failure (1), bronchiolitis obliterans syndrome (2), and solid tumor malignancies (2). CONCLUSIONS: Our results indicate that LLT is associated with comparable survival to other LLT series and provides a granular assessment of infectious and rejection rates in this rare population.

Elevated HbA1c in donor organs from patients without a diagnosis of diabetes portends worse liver allograft survival.

Recipients of liver allografts from diabetic donors have decreased graft survival. However, limited data exist on the effects of donor HbA1c. We hypothesized that allografts from nondiabetic donors with elevated HbA1c would be associated with decreased survival. Liver transplant recipients from the UNOS database from nondiabetic donors were stratified into two groups: euglycemic (HbA1c<6.5) and hyperglycemic (HbA1c≥6.5). Propensity score matching (10:1) was used to adjust for donor and recipient characteristics. Kaplan-Meier analysis was used to assess survival. Donors of hyperglycemic allografts were older (49 vs 36, P<.001), were more likely to be non-white, had a higher BMI (29.8 vs 26.2, P<.001), were more likely to engage in heavy cigarette use (1.5% vs 1.3%, P=.004), had higher serum creatinine levels (1.3 vs 1.0, P=.002), and were more likely to be an expanded-criteria donor (35.8% vs 14.4%, P<.001). After propensity matching to account for these differences, allograft survival was significantly decreased in the recipients of hyperglycemic allografts (P=.049), and patient survival showed a trend toward reduction (P=.082). These findings suggest that HbA1c may be a simple and inexpensive test with potential utility for better organ risk stratification.

Association Between Incomplete Neoadjuvant Radiotherapy and Survival for Patients With Locally Advanced Rectal Cancer.

Importance: Failing to complete chemotherapy adversely affects survival in patients with colorectal cancer. However, the effect of incomplete delivery of neoadjuvant radiotherapy is unclear. Objective: To determine whether incomplete radiotherapy delivery is associated with worse clinical outcomes and survival. Design, Setting, and Participants: Data on 17 600 patients with stage II to III rectal adenocarcinoma from the 2006-2012 National Cancer Database who received neoadjuvant chemoradiotherapy followed by surgical resection were included. Multivariable regression methods were used to compare resection margin positivity, permanent colostomy rate, 30-day readmission, 90-day mortality, and overall survival between patients who received complete (45.0-50.4 Gy) and incomplete (<45.0 Gy) doses of radiation as preoperative therapy. Main Outcomes and Measures: The primary outcome measure was overall survival; short-term perioperative and oncologic outcomes encompassing margin positivity, permanent ostomy rate, postoperative readmission, and postoperative mortality were also assessed. Results: Among 17 600 patients included, 10 862 were men, with an overall median age of 59 years (range, 51-68 years). Of these, 874 patients (5.0%) received incomplete doses of neoadjuvant radiation. The median radiation dose received among those who did not achieve complete dosing was 34.2 Gy (interquartile range, 19.8-40.0 Gy). Female sex (adjusted odds ratio [OR] 0.69; 95% CI, 0.59-0.81; P < .001) and receiving radiotherapy at a different hospital than the one where surgery was performed (OR, 0.72; 95% CI, 0.62-0.85; P < .001) were independent predictors of failing to achieve complete dosing; private insurance status was predictive of completing radiotherapy (OR, 1.60; 95% CI, 1.16-2.21; P = .004). At 5-year follow-up, overall survival was improved among patients who received a complete course of radiotherapy (3086 [estimated survival probability, 73.2%] vs 133 [63.0%]; P < .001). After adjustment for demographic, clinical, and tumor characteristics, patients receiving a complete vs incomplete radiation dose had a similar resection margin positivity (OR, 0.99; 95% CI, 0.72-1.35; P = .92), permanent colostomy rate (OR, 0.96; 95% CI, 0.70-1.32; P = .81), 30-day readmission rate (OR, 0.92; 95% CI, 0.67-1.27; P = .62), and 90-day mortality (OR, 0.72; 95% CI, 0.33-1.54; P = .41). However, a complete radiation dose had a significantly lower risk of long-term mortality (adjusted hazard ratio, 0.70; 95% CI, 0.59-0.84; P < .001). Conclusions and Relevance: Achieving a target radiation dose of 45.0 to 50.4 Gy is associated with a survival benefit in patients with locally advanced rectal cancer. Aligning all aspects of multimodal oncology care may increase the probability of completing neoadjuvant therapy.

Comparison of surgical outcomes after anterior cervical discectomy and fusion: does the intra-operative use of a microscope improve surgical outcomes.

BACKGROUND: The primary aim of this study was to assess and compare the complications profile as well as long-term clinical outcomes between patients undergoing an Anterior Cervical Discectomy and Fusion (ACDF) procedure with and without the use of an intra-operative microscope. METHODS: One hundred and forty adult patients (non-microscope cohort: 81; microscope cohort: 59) undergoing ACDF at a major academic medical center were included in this study. Enrollment criteria included available demographic, surgical and clinical outcome data. All patients had prospectively collected patient-reported outcomes measures and a minimum 2-year follow-up. Patients completed the neck disability index (NDI), short-form 12 (SF-12) and visual analog pain scale (VAS) before surgery, then at 3, 6, 12, and 24 months after surgery. Clinical outcomes and complication rates were compared between both patient cohorts. RESULTS: Baseline characteristics were similar between both cohorts. The mean ± standard deviation duration of surgery was longer in the microscope cohort (microscope: 169±34 minutes vs. non-microscope: 98±42 minutes, P<0.001). There was no significant difference between cohorts in the incidence of nerve root injury (P=0.99) or incidental durotomy (P=0.32). At 3 months post-operatively, both cohorts demonstrated similar improvement in VAS-neck pain (P=0.69), NDI (P=0.86), SF-12 PCS (P=0.84) and SF-12 MCS (P=0.75). At 2-year post-operatively, both the microscope and non-microscope cohorts demonstrated similar improvement from base line in NDI (microscope: 13.52±25.77 vs. non-microscope: 19.51±27.47, P<0.18), SF-12 PCS (microscope: 4.15±26.39 vs. non-microscope: 11.98±22.96, P<0.07), SF-12 MCS (microscope: 9.47±32.38 vs. non-microscope: 16.19±30.44, P<0.21). Interestingly at 2 years, the change in VAS neck pain score was significantly different between cohorts (microscope: 2.22±4.00 vs. non-microscope: 3.69±3.61, P<0.02). CONCLUSIONS: Our study demonstrates that the intra-operative use of a microscope does not improve overall surgery-related outcomes, nor does it lead to superior long-term outcomes in pain and functional disability, 2 years after index surgery.