Resection of the Primary Tumor and Survival in Patients with Single-Site Synchronous Oligometastatic Non-Small Cell Lung Cancer: Propensity-Matched Analysis of the National Cancer Database.

BACKGROUND: Local therapy for the primary tumor is postulated to remove resistant cancer cells as well as immunosuppressive cells from the tumor microenvironment, potentially improving response to systemic therapy (ST). We sought to determine whether resection of the primary tumor was associated with overall survival (OS) in a multicentric cohort of patients with single-site synchronous oligometastatic non-small cell lung cancer. STUDY DESIGN: Using the National Cancer Database (2018 to 2020), we evaluated patients with clinical stage IVA disease who received ST and stratified the cohort based on receipt of surgery for the primary tumor (S). We used multivariable and propensity score-matched analysis to study factors associated with S (logistic regression) and OS (Cox regression and Kaplan-Meier), respectively. RESULTS: Among 12,215 patients identified, 2.9% (N = 349) underwent S and 97.1% (N = 11,886) ST (chemotherapy or immunotherapy) without surgery. Patients who underwent S were younger, more often White, had higher income levels, were more likely to have private insurance, and were more often treated at an academic facility. Among those who received S, 22.9% (N = 80) also underwent resection of the distant metastatic site. On multivariable analysis, metastasis to bone, N+ disease, and higher T-stages were independently associated with less S. On Cox regression, S and resection of the metastatic site were associated with improved survival (hazard ratio 0.67, 95% CI 0.56 to 0.80 and hazard ratio 0.80, 95% CI 0.72 to 0.88, respectively). After propensity matching, OS was improved in patients undergoing S (median 36.8 vs 20.8 months, log-rank p < 0.001). CONCLUSIONS: Advances in ST for non-small cell lung cancer may change the paradigm of eligibility for surgery. This study demonstrates that surgical resection of the primary tumor is associated with improved OS in selected patients with single-site oligometastatic disease.

SIRT1 Prevents R-Loops during Chronological Aging by Modulating DNA Replication at rDNA Loci.

In metazoans, the largest sirtuin, SIRT1, is a nuclear protein implicated in epigenetic modifications, circadian signaling, DNA recombination, replication, and repair. Our previous studies have demonstrated that SIRT1 binds replication origins and inhibits replication initiation from a group of potential initiation sites (dormant origins). We studied the effects of aging and SIRT1 activity on replication origin usage and the incidence of transcription-replication collisions (creating R-loop structures) in adult human cells obtained at different time points during chronological aging and in cancer cells. In primary, untransformed cells, SIRT1 activity declined and the prevalence of R-loops rose with chronological aging. Both the reduction in SIRT1 activity and the increased abundance of R-loops were also observed during the passage of primary cells in culture. All cells, regardless of donor age or transformation status, reacted to the short-term, acute chemical inhibition of SIRT1 with the activation of excessive replication initiation events coincident with an increased prevalence of R-loops. However, cancer cells activated dormant replication origins, genome-wide, during long-term proliferation with mutated or depleted SIRT1, whereas, in primary cells, the aging-associated SIRT1-mediated activation of dormant origins was restricted to rDNA loci. These observations suggest that chronological aging and the associated decline in SIRT1 activity relax the regulatory networks that protect cells against excess replication and that the mechanisms protecting from replication-transcription collisions at the rDNA loci manifest as differentially enhanced sensitivities to SIRT1 decline and chronological aging.

Is underutilization of adjuvant therapy in resected non-small-cell lung cancer associated with socioeconomic disparities?

OBJECTIVES: Although adjuvant systemic therapy (AT) has demonstrated improved survival in patients with resected non-small-cell lung cancer (NSCLC), it remains underutilized. Recent trials demonstrating improved outcomes with adjuvant immunotherapy and targeted treatment imply that low uptake of systemic therapy in at-risk populations may widen existing outcome gaps. We, therefore, sought to determine factors associated with the underutilization of AT. METHODS: The National Cancer Database (2010-2018) was queried for patients with completely resected stage II-IIIA NSCLC and stratified based on the receipt of AT. Logistic regression was used to identify factors associated with AT delivery. The Kaplan-Meier method was applied to estimate survival after propensity-matching to adjust for confounders. RESULTS: Of 37 571 eligible patients, only 20 616 (54.9%) received AT. While AT rates increased over time, multivariable analysis showed that older age [adjusted odds ratio (aOR) 0.45, 95% confidence interval (CI) 0.43-0.47], male sex (aOR 0.88, 95% CI 0.85-0.93) and multiple comorbidities (aOR 0.86, 95% CI: 0.81-0.91) were associated with decreased AT. Socioeconomic factors were additionally associated with underutilization, including public insurance (aOR 0.70, 95% CI: 0.66-0.74), lower education indicators (aOR 0.93, 95% CI: 0.88-0.97) and living more than 10 miles from a treatment facility (aOR 0.89, 95% CI: 0.85-0.93). After propensity matching, receipt of adjuvant therapy was associated with improved overall survival (median 76.35 vs 47.57 months, P ≤ 0.001). CONCLUSIONS: AT underutilization in patients with resected stage II-III NSCLC is associated with patient, institutional and socioeconomic factors. It is critical to implement measures to address these inequities, especially in light of newer adjuvant immunotherapy and targeted therapy treatment options which are expected to improve survival.

Proximal aortic repair in dialysis patients: A national database analysis.

OBJECTIVES: Dialysis is a well-established risk factor for morbidity and mortality after cardiovascular procedures. However, little is known regarding the outcomes of proximal aortic surgery in this high-risk cohort. METHODS: Perioperative (in-hospital or 30-day mortality) and 10-year outcomes were analyzed for all the patients who underwent open proximal aortic repair with the diagnosis of nonruptured thoracic aortic aneurysm (aneurysm, n = 325) or type A aortic dissection (dissection, n = 461) from 1987 to 2015 using the US Renal Data System database. RESULTS: In patients with aneurysm, perioperative mortality was 12.6%. The 10-year mortality was 81% ± 3%. Age 65 years or more (hazard ratio [HR], 1.35; 95% confidence interval [CI], 1.03 to 1.78; P = .03), chronic obstructive pulmonary disease (HR, 1.68; 95% CI, 1.01-2.82; P = .047), and Black race (HR, 1.46; 95% CI, 1.09-1.97; P = .01) were independently associated with worse 10-year mortality. In patients with dissection, perioperative mortality was 24.3% and 10-year mortality was 87.9% ± 2.2%. Age 65 years or more (HR, 1.49; 95% CI, 1.19-1.86; P < .001), congestive heart failure (HR, 1.39; 95% CI, 1.11-2.57; P = .004), and diabetes mellitus as the cause of dialysis (HR, 1.75; 95% CI, 1.2-2.57; P = .004) were independently associated with worse 10-year mortality. Black race (HR, 0.74; 95% CI, 0.6-0.92; P = .008) was associated with a better outcome. CONCLUSIONS: We described challenging perioperative and 10-year outcomes for dialysis patients undergoing proximal aortic repair. The present study suggests the need for careful patient selection in the elective repair of proximal aortic aneurysm for dialysis-dependent patients, whereas it affirms the feasibility of emergency surgery for acute type A aortic dissections.

Three-year survival of transcatheter versus surgical aortic valve replacement in dialysis.

To highlight the trends of surgical (open) aortic valve replacement (SAVR) as well as to compare the outcome between transcatheter aortic valve replacement (TAVR) and SAVR in elderly dialysis patients. TAVR has evolved as an effective alternative to surgery (SAVR) for aortic stenosis. We identified dialysis-dependent patients who underwent SAVR or TAVR from 2000 to 2015 from the United States Renal Data System using ICD-9 codes. We defined high-risk surgical patients as age over 70 or older. The primary endpoint was survival at 3 years and we compared the outcome between SAVR and TAVR groups using inverse probability of treatment weighting (IPTW). A total of 4332 and 1280 dialysis patients underwent SAVR and TAVR, respectively, during the study period. Among SAVR cohort, 3312 patients underwent SAVR before June 2012 and 1020 after June 2012. In-hospital mortality was significantly worse before 2012 (14.6% vs. 11.3% after 2012, p = 0.007) as well as estimated 3-year mortality (69.1% vs. 60.3% after 2012, p < 0.001). After June 2012, the TAVR cohort was older and had more comorbidities including coronary artery disease and congestive heart failure compared to the SAVR cohort. After IPTW, in-hospital mortality was significantly lower after TAVR versus SAVR (odds ratio 0.38 [95% confidence interval [CI], 0.27-0.52], p < 0.001). However, TAVR had a significantly higher risk of 3-year mortality than SAVR (hazard ratio 1.24 [95% CI 1.1-1.39], p < 0.001). TAVR may be a reasonable and potentially preferable alternative to SAVR in the elderly dialysis population in the short-term period.

Implementing a High-Value Care Discharge Protocol in Patients Undergoing CABG Reduces Readmission.

BACKGROUND: Readmission after coronary artery bypass grafting (CABG) is associated with adverse outcomes and increased cost. We evaluated the impact of a high-value care discharge protocol on readmission, length of stay (LOS), and discharge destination in patients undergoing isolated CABG. METHODS: In 2016, a comprehensive, patient-centered discharge protocol was implemented. A nurse practitioner was the fulcrum of this program, which focused on improving health literacy, disease management, and rigorous follow-up. All patients undergoing isolated CABG between 2012 and 2019 were retrospectively analyzed with regard to 30-day readmission, LOS, and discharge disposition. Differences were analyzed by Mann-Whitney, chi-square, and t tests. Analyses were repeated using propensity matching. RESULTS: A total of 910 consecutive patients undergoing isolated CABG were included in the analyses: 353 preprotocol and 557 postprotocol. Preprotocol patients had a readmission rate of 14.4% (n = 51), compared with 6.8% (n = 38) in the postprotocol patients (P < .001). Median postoperative LOS before implementation was 6 (interquartile range, 5-8) days compared with 5 (interquartile range, 4-6) days postimplementation (P < .001). Postimplementation, a higher proportion of patients were discharged to home compared with a skilled nursing facility (82.7% [n = 461] vs 73.9% [n = 261]; P = .002). After propensity matching, 298 well-balanced patients were included for analysis and these significant reductions in LOS, readmission, and discharge destination persisted. CONCLUSIONS: Implementation of a new discharge protocol was significantly associated with reduced readmission and LOS, along with higher rates of discharge to home in isolated CABG patients. Importantly, the results were sustainable and did not require additional resources, delivering high-value care.

Rib fixation in geriatric trauma: Mortality benefits for the most vulnerable patients.

BACKGROUND: Rib fractures in the geriatric trauma population are associated with significant morbidity and mortality. The outcomes of surgical stabilization of rib fractures (SSRF) have not been well defined in this population. METHODS: Data from the 2016 to 2017 Trauma Quality Improvement Program database were analyzed. Patients older than 65 years admitted with isolated chest wall injury and multiple rib fractures were abstracted from the database. Multivariate propensity score matching was utilized to stratify patients that underwent rib fixation versus nonoperative management. In the matched cohort, we assessed outcomes including mortality, intensive care unit (ICU) and hospital lengths of stay (LOS), tracheostomy rates, and ventilator-associated pneumonia (VAP) rates. We performed a secondary analysis of patients receiving early (<72 hours) versus late SSRF. RESULTS: Of the 44,450 patients included in the study analysis, 758 (1.7%) underwent SSRF. Patients undergoing SSRF were younger, had a higher prevalence of flail chest, higher rates of emergency room intubation, higher Injury Severity Score, and increased ICU admission rates. The 1:1 propensity score match resulted in 758 patients in each group. The in-hospital mortality rate was significantly lower in patients that underwent SSRF (4.2% vs. 7.3%, p = 0.01). However, the fixation group also had higher rates of tracheostomy during admission (11.2% vs. 4.6%, p < 0.001) and VAP (3.0% vs. 1.6%, p = 0.007). In a secondary matched analysis of 326 pairs of patients undergoing SSRF, we found that early fixation was associated with decreased rates of VAP (1.5% vs. 4.6%, p = 0.01), fewer ventilator days (4 days vs. 7 days, p = 0.003), shorter ICU LOS (6 days vs. 9 days, p = 0.001), and shorter hospital LOS (10 days vs. 15 days, p < 0.001). CONCLUSION: This study demonstrates a mortality benefit in geriatric trauma patients undergoing SSRF. Early SSRF was observed to be associated with decreased rates of VAP, decreased ICU LOS, and decreased hospital LOS. Early SSRF may be associated with improved outcomes in the geriatric trauma population with multiple rib fractures. LEVEL OF EVIDENCE: Therapeutic/Care management, level III.

Intraoperative Autologous Blood Donation Leads to Fewer Transfusions in Cardiac Surgery.

BACKGROUND: Blood conservation with antifibrinolytics, topical hemostatics, and strict transfusion triggers are becoming commonplace in cardiac surgery. The aim of this study was to evaluate the effect of a blood conservation protocol centering on standardized intraoperative autologous blood donation (IAD) use in cardiac surgery. METHODS: We reviewed charts of patients who underwent cardiac surgery at our hospital over an 8-year period to analyze transfusion tendencies before and after a new blood conservation policy was implemented. Propensity score matching was used to account for population differences in preoperative and perioperative covariates. RESULTS: Over an 8-year period (January 2009 to December 2017) 1002 patients were studied. Three hundred fifty-two patients before the new blood conservation policy (group 1) were compared with 650 patients after the change (group 2). Fewer group 2 patients required blood transfusions during their hospital stay (78% vs 61%, P < .001), were transfused fewer units (2.8 vs 1.81 units, P < .001), and experienced a shorter length of stay (8.02 vs 7.28 days, P = .012). Propensity score-matched cohorts revealed reductions in any complication (29.5% vs 18.8%, P = .007), fewer postoperative transfusions (70.1% vs 50.9%, P < .001), and a lower transfusion volume (1.82 vs 1.21 units, P = .002) associated with IAD without any associated change in mortality. CONCLUSIONS: IAD use is associated with reduced transfusions in cardiac surgery and may be considered a complementary aspect of blood conservation. Our experience suggests it may be applied with few limitations. A causal relationship between IAD and outcomes should be established with prospective studies.

Coexisting DCIS and phyllodes breast tumors in Young Chinese women: Case series.

INTRODUCTION: Breast cystosarcoma phyllodes tumors are rare and can be benign or malignant. All sub-divisions of phyllodes tumor-benign, borderline and malignant, can harbor carcinomas, although the incidence is extremely rare. METHODS: We present two nonconsecutive cases of coexisting ductal carcinoma in situ (DCIS) and phyllodes breast tumors in young patients. METHODS & CASE PRESENTATION: Retrospective review of two patient's medical record was performed. CASE 1: 30-year-old female underwent excisional biopsy for 3.48 cm mass found on ultrasound. Pathology revealed malignant phyllodes tumor with positive margin. On re-excision, patient was found to have 1.5 cm area of ductal carcinoma in situ (DCIS) with positive margin. Patient then underwent re-reexicision of DCIS with negative margin. Patient underwent chemotherapy and tamoxifen for three years without evidence of disease. CASE 2: 30-year-old female presented with 1.3 cm lesion found on ultrasound which core needle biopsy revealed a fibroepithelial tumor. Patient subsequently underwent excision biopsy which found 1.5 cm benign phyllodes tumor and 3.5 mm DCIS within the phyllodes tumor with negative margins. Patient declined additional chemotherapy or hormonal therapy and is currently considering mastectomy. CONCLUSION: Phyllodes tumors are rare and ones with a coexisting carcinoma are even less frequently encountered. The treatment plan can change upon diagnosis of the carcinoma via the pathology. Treatment should be guided by the type and stage of carcinoma detected which may include additional surgical resection and lymph node sampling.

A case report of parotid mammary analogue secretory carcinoma and reviews.

INTRODUCTION: Mammary analog secretory carcinoma (MASC) is a new diagnosis of head and neck tumors first reported in 2010. It was often misdiagnosed as salivary acinic cell carcinoma (AciCC). We present a patient with an asymptomatic parotid tumor that underwent deep lobe parotidectomy and postoperative radiation therapy. The final pathology showed MASC. CASE PRESENTATION: A 57-year-old male presented with an asymptomatic enlarging right parotid mass. A CT neck with IV contrast showed a 1.2 cm heterogeneously enhancing mass in the center of the right parotid gland without extraparotid extension. An FNA showed an epithelial neoplasm with papillary features. The patient underwent a right deep lobe parotidectomy with facial nerve dissection. The final pathology confirmed the diagnosis of MASC. He subsequently completed a 6-week course of radiation therapy and remained asymptomatic at his 30-month follow up. DISCUSSION/CONCLUSION: Although MASC is considered a low-grade tumor in most cases, recurrence and disseminated disease are not uncommon. No standard treatment protocol has been established. This report aims to enhance the awareness of this diagnosis and provide a review of current treatments for head and neck oncology care providers.

Sebaceous lymphadenoma requiring superficial parotidectomy.

An 82-year-old woman presented with a painless, progressively enlarging right neck mass of 2 years' duration. CT with contrast showed a 5.0 cm confluence of nodes just inferior to the right parotid gland. Fine-needle aspiration showed a lymphoproliferative disorder. Incisional biopsy showed sebaceous lymphadenoma. She subsequently underwent superficial right parotidectomy with neck dissection of level II-V (performed for enlarged lymph nodes causing significant pain). Facial nerve was preserved. She remained free of disease nearly 1 year postoperatively.

Survival benefits in colorectal adenocarcinoma with the use of metformin among a black diabetic inner city population.

We assessed the association of metformin use with survival in colorectal cancer in a population consists mostly of African-American and Afro-Caribbean patients. We identified 585 colorectal cancer patients, 167 (28.6%) and 418 (71.5%) were as diabetic (DM) and nondiabetic, respectively. The diagnosis of diabetes did not impact cancer survival or extent of disease. Overall, DMs with metformin use (D+M+) have better overall survival than both DMs without metformin use (D+M∼) and nondiabetics (D∼M∼), with a mean survival of 109.9 months compared with 95.7 and 106.1 months, respectively (log-rank p < 0.05). The use of metformin shows significant reduction of risk of mortality compared with nonusers (hazard ratio: 0.34; 95% CI: 0.15-0.81; p = 0.01). Use of insulin and status of diabetes did not have a significant impact on overall cancer survival.

A rare case of splenic pseudoaneurysm in pediatric splenic blunt trauma patient: Review of diagnosis and management.

INTRODUCTION: Splenic pseudoaneurysms (SPA) are a rare but serious sequela of blunt traumatic injury to the spleen. Management of adult blunt splenic trauma is well-studied, however, in children, the management is much less well-defined. PRESENTATION OF CASE: A 15 year-old male presented with severe abdominal pain of acute onset after sustaining injury to his left side while playing football. FAST was positive for free fluid in the abdomen. Initial abdomen CT demonstrated a grade III/IV left splenic laceration with moderate to large hemoperitoneum with no active extravasation or injury to the splenic vessels noted. A follow-up CT angiography of the abdomen demonstrated a splenic hypervascular structure suspicious for a small pseudoaneurysm. Splenic arteriogram which demonstrated multiple pseudoaneurysms arising from the second order splenic artery branches which was angioembolized and treated. DISCUSSION & CONCLUSION: Questions still remain regarding the timing of repeat imaging for diagnosis of SPA following non-operative blunt splenic trauma, which patients should be imaged, and how to manage SPA upon diagnosis. More clinical study and basic science research is warranted to study the disease process of SPA in pediatric patient. We believe that our proposed management algorithm timely detect formation of delayed SPA formation and addresses the possible fatal disease course of pediatric SPA.