Association of Systemic Chemotherapy Approaches With Outcomes in Appendiceal Peritoneal Metastases.

INTRODUCTION: Many patients undergoing cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) for appendiceal adenocarcinoma peritoneal metastases (APM) undergo preoperative systemic chemotherapy. The primary aim of this study is to evaluate differences in oncologic outcomes among two popular chemotherapy approaches in patients with APM undergoing CRS-HIPEC. METHODS: We performed a multicenter retrospective review of patients who underwent CRS-HIPEC for APM due to high or intermediate grade disease between 2013 and 2019. Patients in the total neoadjuvant therapy group (TNT) received 12 cycles of preoperative chemotherapy. Patients in the "sandwich" chemotherapy group (SAND) received six cycles of preoperative chemotherapy with a maximum of six cycles of postoperative chemotherapy. The primary outcomes were overall survival (OS) and recurrence-free survival (RFS) defined as months from date of first treatment or surgery, respectively. RESULTS: A total of 39 patients were included in this analysis, with 25 (64%) patients in the TNT group and 14 (36%) patients in the SAND group. Patients in the TNT group had a median OS of 62 mo, while median OS in the SAND group was 45 mo (P = 0.01). In addition, patients in the TNT group had significantly longer RFS compared to the SAND group (35 versus 12 mo, P = 0.03). In a multivariable analysis, TNT approach was independently associated with improved OS and RFS. CONCLUSIONS: In this multicenter retrospective analysis, a TNT approach was associated with improved overall and recurrence-free survival compared to a sandwiched chemotherapy approach in patients undergoing CRS-HIPEC for high or intermediate grade APM.

A total neoadjuvant chemotherapy approach is associated with improved recurrence-free survival in patients with colorectal peritoneal metastases undergoing cytoreductive surgery and HIPEC.

BACKGROUND: The primary aim of this study is to evaluate the oncologic outcomes of two popular systemic chemotherapy approaches in patients with colorectal peritoneal metastases (CPM) undergoing cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC). METHODS: We performed a dual-center retrospective review of consecutive patients who underwent CRS-HIPEC for CPM due to high or intermediate-grade colorectal cancer. Patients in the total neoadjuvant therapy (TNT) group received 6 months of preoperative chemotherapy. Patients in the "sandwich" (SAND) chemotherapy group received 3 months of preoperative chemotherapy with a maximum of 3 months of postoperative chemotherapy. RESULTS: A total of 34 (43%) patients were included in the TNT group and 45 (57%) patients in the SAND group. The median overall survival (OS) in the TNT and SAND groups were 77 and 61 months, respectively (p = 0.8). Patients in the TNT group had significantly longer recurrence-free survival (RFS) than the SAND group (29 vs. 12 months, p = 0.02). In a multivariable analysis, the TNT approach was independently associated with improved RFS. CONCLUSION: In this retrospective study, a TNT approach was associated with improved RFS, but not OS when compared with a SAND approach. Further prospective studies are needed to examine these systemic chemotherapeutic approaches in patients with CPM undergoing CRS-HIPEC.

A comprehensive framework for early-onset colorectal cancer research.

Sporadic colorectal cancer has traditionally been viewed as a malignancy of older individuals. However, as the global prevalence of the disease diagnosed in younger individuals (<50 years) is expected to increase within the next decade, greater recognition is now being given to early-onset colorectal cancer. The cause of the predicted rise in prevalence is largely unknown and probably multifactorial. In this Series paper, we discuss the potential underlying causes of early-onset colorectal cancer, the role of energy balance, biological and genomic mechanisms (including microbiome aspects), and the treatment of early-onset colorectal cancer. We have specifically considered the psychosocial challenges of being diagnosed with colorectal cancer at younger age and the potential financial toxicity that might ensue. This Series paper brings a comprehensive review based on the existing data in the hopes of optimising the overall outcomes for patients with early-onset colorectal cancer.

Outcomes of robotic-assisted liver surgery versus laparoscopic liver surgery for treatment of stage I hepatocellular carcinoma.

BACKGROUND: This article investigated whether robotic-assisted liver surgery versus laparoscopic liver surgical treatment of hepatocellular carcinoma (HCC) has similar or different short- and long-term clinical outcomes. METHODS: A total of 3049 patients from the National Cancer Database who received minimally invasive surgery (ie, robotic or laparoscopic surgery) for stage I HCC cancers between 2010 to 2015, of which 123 had robotic and 2926 had laparoscopic surgeries performed, were identified. Logistic regression was applied to evaluate short-term outcomes. Cox proportional hazards models were applied to estimate all-cause mortality at 1-year, 3-years, and 5-years after surgery, adjusting for potential confounders. Propensity score-matched analyses were conducted to compare long-term outcomes between robotic and laparoscopic surgeries. RESULTS: Robotic surgery was associated with improved overall survival, with 1-, 3-, and 5-year survival rates (SRs) of 0.92, 0.75, and 0.63 compared with laparoscopic surgery SRs of 0.86, 0.60, and 0.45, respectively (P value <.01). Multivariate analyses showed that robotic compared with laparoscopic surgery had significantly lower 5-year total mortality (hazard ratio [HR], 0.64 and 95% confidence interval [CI], 0.45%-0.93% for intent-to-treat; HR, 0.62 and 95% CI, 0.42%-0.91% for end-treatment analyses). Similar results were found in propensity score matched analyses; robotic surgery was associated with improved overall survival compared with laparoscopic surgery (HR, 0.64 and 95% CI, 0.43%-0.96% for intent-to-treat; HR, 0.59 and 95% CI, 0.39%-0.90% for end-treatment). CONCLUSIONS: Robotic surgery is not inferior to laparoscopic surgery in treating early-stage HCC and may be associated with improved long-term survival.

Longitudinal transcriptional analysis of peripheral blood leukocytes in COVID-19 convalescent donors.

BACKGROUND: SARS-CoV2 can induce a strong host immune response. Many studies have evaluated antibody response following SARS-CoV2 infections. This study investigated the immune response and T cell receptor diversity in people who had recovered from SARS-CoV2 infection (COVID-19). METHODS: Using the nCounter platform, we compared transcriptomic profiles of 162 COVID-19 convalescent donors (CCD) and 40 healthy donors (HD). 69 of the 162 CCDs had two or more time points sampled. RESULTS: After eliminating the effects of demographic factors, we found extensive differential gene expression up to 241 days into the convalescent period. The differentially expressed genes were involved in several pathways, including virus-host interaction, interleukin and JAK-STAT signaling, T-cell co-stimulation, and immune exhaustion. A subset of 21 CCD samples was found to be highly "perturbed," characterized by overexpression of PLAU, IL1B, NFKB1, PLEK, LCP2, IRF3, MTOR, IL18BP, RACK1, TGFB1, and others. In addition, one of the clusters, P1 (n = 8) CCD samples, showed enhanced TCR diversity in 7 VJ pairs (TRAV9.1_TCRVA_014.1, TRBV6.8_TCRVB_016.1, TRAV7_TCRVA_008.1, TRGV9_ENST00000444775.1, TRAV18_TCRVA_026.1, TRGV4_ENST00000390345.1, TRAV11_TCRVA_017.1). Multiplexed cytokine analysis revealed anomalies in SCF, SCGF-b, and MCP-1 expression in this subset. CONCLUSIONS: Persistent alterations in inflammatory pathways and T-cell activation/exhaustion markers for months after active infection may help shed light on the pathophysiology of a prolonged post-viral syndrome observed following recovery from COVID-19 infection. Future studies may inform the ability to identify druggable targets involving these pathways to mitigate the long-term effects of COVID-19 infection. TRIAL REGISTRATION: https://clinicaltrials.gov/ct2/show/NCT04360278 Registered April 24, 2020.

Impact of Insurance Status on Oncologic and Perioperative Outcomes After Cytoreductive Surgery with Hyperthermic Intraperitoneal Chemotherapy.

BACKGROUND: A growing body of research has shown that underinsured patients are at increased risk of worse health outcomes compared with insured patients. Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) is largely performed at highly specialized cancer centers and may pose challenges for the underinsured. This study investigates surgical outcomes following CRS-HIPEC for insured and underinsured patients with peritoneal carcinomatosis. METHODS: We performed a retrospective cohort study of 125 patients undergoing CRS-HIPEC between 2013 and 2019. Patients were categorized into two groups. The insured group was comprised of patients with private insurance at the time of CRS-HIPEC or who obtained it during the follow-up period. The underinsured group consisted of patients with Medicaid, or self-pay. Perioperative and oncologic outcomes were compared between the two groups. RESULTS: A total of 102 (82.3%) patients were insured, and 22 (17.7%) patients were underinsured. There were no significant differences in age, medical morbidities, primary tumor characteristics, peritoneal carcinomatosis index, or completion of cytoreduction score between the two groups. The median overall survival (OS) for insured patients was 64.8 months and was 52.9 months for underinsured patients (p = 0.01). Additionally, insured patients had a significantly longer follow-up time. Underinsurance status also was associated with increased hospital and intensive care unit length of stay, and higher rate of Clavien-Dindo classification III-IV complications. CONCLUSIONS: In this retrospective study conducted at a large, urban, specialized cancer center, private insurance status was associated with increased overall survival and longer follow-up period. Furthermore, underinsurance status was associated with increased perioperative morbidity.

Radiotherapy after breast-conserving surgery for elderly patients with early-stage breast cancer: A national registry-based study.

Considerable controversies exist regarding whether elderly patients with early-stage breast cancer receiving breast-conserving surgery (BCS) should forgo radiotherapy. We utilized the National Cancer Database to analyze data of 115 516 women aged ≥70 years, treated with BCS for T1-2N0-1M0 breast cancer between 2004 and 2014. Multivariable Cox proportional hazards model was used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for mortality 3, 5 and 10 years after 90 days of BCS associated with radiotherapy. Patients who received no radiotherapy had a higher mortality rate than those who received radiotherapy (5-year survival rate: 71.2% vs 83.8%), with multivariable-adjusted HRs of 1.65 (95% CI: 1.57-1.72) for 3-year mortality, 1.53 (1.47-1.58) for 5-year mortality and 1.43 (1.39-1.48) for 10-year mortality. The association held even for patients ≥90 years. This association was observed in all strata by reasons for radiotherapy omission, receipt of endocrine therapy or chemotherapy, calendar period and other clinical characteristics, with 40% to 65% increased 5-year mortality for patients without radiotherapy. This positive association persisted when analyses were restricted to patients with T1N0 and estrogen-receptor-positive disease who had received endocrine therapy (5-year mortality: HR 1.47 [1.39-1.57]) and in propensity score weighted analyses. Our study shows, in routine practice, elderly patients who received no post-BCS radiotherapy had higher total mortality than those who received radiotherapy. These findings suggest that the current recommendation of omission of post-BCS radiotherapy for elderly women with early-stage breast cancer may need to be reconsidered, particularly for those without contraindication.

Adherence to treatment guidelines as a major determinant of survival disparities between black and white patients with ovarian cancer.

OBJECTIVE: To evaluate whether non-adherence to National Comprehensive Cancer Network (NCCN) treatment guidelines and other factors related to treatment access contribute to racial disparities in ovarian cancer survival. METHODS: This large cohort study included patients from the National Cancer Database who were diagnosed with ovarian cancer between 2004 and 2014, with follow-up data up to 2017. The multivariable Cox regression was used to assess the effect of study variables on five-year overall survival. The proportion contributions of prognostic factors to the survival disparities were estimated using individual and sequential adjustment of these factors based on the Cox proportional hazards models. RESULTS: Of the 120,712 patients eligible for this study, 110,032 (91.1%) were whites and 10,680 (8.9%) were blacks. Black patients, compared with their white counterparts, had a lower adherence to NCCN guidelines (60.8% vs. 70.4%, respectively, P < 0.001), and a higher five-year mortality after cancer diagnosis (age- and tumor characteristics- adjusted hazard ratio: 1.22, 95% confidence interval: 1.19-1.25). Non-adherence to NCCN treatment guidelines was the most significant contributor to racial disparity in ovarian cancer survival, followed by access to care and comorbidity, each explaining 36.4%, 22.7%, and 18.2% of the racial differences in five-year overall survival, respectively. These factors combined explain 59.1% of racial survival disparities. Risk factors identified for non-adherence to treatment guidelines among blacks include insurance status, treatment facility type, educational attainment, age, and comorbidity. CONCLUSIONS: Adherence status to NCCN treatment guidelines is the most important contributor to the survival disparities between black and white patients with ovarian cancer. Our findings call for measures to promote equitable access to guideline-adherence care to improve the survival of black women with ovarian cancer.

Primary Tumor Resection Offers Survival Benefit in Patients with Metastatic Midgut Neuroendocrine Tumors.

BACKGROUND: Approximately 35% of patients with midgut neuroendocrine tumors (MNET) present with distant metastases. Although successful resection of these metastatic foci improves overall survival (OS), the role of primary tumor resection (PTR) in patients with unresectable metastatic disease is unclear. The aim of this study is to evaluate prevalence and survival impact of PTR in patients with unresectable metastatic MNET. PATIENTS AND METHODS: A retrospective cohort study of patients with metastatic MNET was performed using the National Cancer Database (2004-2014). Demographic and clinicopathologic variables were compared between patients who did and did not undergo PTR. Survival analysis was performed using Kaplan-Meier and log-rank tests. Multivariable regression analysis was used to assess factors associated with PTR and all-cause mortality. RESULTS: The cohort included 4076 patients; 2520 (61.8%) underwent PTR. Patients more likely to undergo PTR were younger and diagnosed earlier, underwent treatment at a nonacademic facility, lived on the West Coast or in the Central USA, and presented with smaller lower-grade small bowel primary tumors. Median OS was improved for patients who underwent PTR compared with those who did not (71 vs. 29 months, p < 0.001). On multivariable analysis, younger age, Black race, higher income, later year of diagnosis, treatment at an academic facility, private insurance, fewer comorbidities, small bowel primary, lower grade, and PTR (hazard ratio 0.63, 95% confidence interval 0.51-0.78, p < 0.001) were associated with lower mortality. CONCLUSIONS: PTR was associated with improved OS. Further study is needed to understand how clinicians select patients for PTR.

Specific Growth Rate as a Predictor of Survival in Pancreatic Neuroendocrine Tumors: A Multi-institutional Study from the United States Neuroendocrine Study Group.

BACKGROUND: Pancreatic neuroendocrine tumors (PNETs) are often indolent; however, identifying patients at risk for rapidly progressing variants is critical, particularly for those with small tumors who may be candidates for expectant management. Specific growth rate (SGR) has been predictive of survival in other malignancies but has not been examined in PNETs. METHODS: A retrospective cohort study of adult patients who underwent PNET resection from 2000 to 2016 was performed utilizing the multi-institutional United States Neuroendocrine Study Group database. Patients with ≥ 2 preoperative cross-sectional imaging studies at least 30 days apart were included in our analysis (N = 288). Patients were grouped as "high SGR" or "low SGR." Demographic and clinical factors were compared between the groups. Kaplan-Meier and log-rank analysis were used for survival analysis. Cox proportional hazard analysis was used to assess the impact of various clinical factors on overall survival (OS). RESULTS: High SGR was associated with higher T stage at resection, shorter doubling time, and elevated HbA1c (all P ≤ 0.01). Patients with high SGR had significantly decreased 5-year OS (63 vs 80%, P = 0.01) and disease-specific survival (72 vs 91%, P = 0.03) compared to those with low SGR. In patients with small (≤ 2 cm) tumors (N = 106), high SGR predicted lower 5-year OS (79 vs 96%, P = 0.01). On multivariate analysis, high SGR was independently associated with worse OS (hazard ratio 2.67, 95% confidence interval 1.05-6.84, P = 0.04). CONCLUSION: High SGR is associated with worse survival in PNET patients. Evaluating PNET SGR may enhance clinical decision-making, particularly when weighing expectant management versus surgery in patients with small tumors.

Impact of Insurance Status on Survival in Gastroenteropancreatic Neuroendocrine Tumors.

BACKGROUND: Insurance status predicts access to medical care in the USA. Previous studies have shown uninsured patients with some malignancies have worse outcomes than insured patients. The impact of insurance status on patients with gastroenteropancreatic neuroendocrine tumors (GEP-NETs) is unclear. PATIENTS AND METHODS: A retrospective cohort study of adult patients with resected GEP-NETs was performed using the US Neuroendocrine Tumor Study Group (USNETSG) database (2000-2016). Demographic and clinical factors were compared by insurance status. Patients ≥ 65 years were excluded, as these patients are almost universally covered by Medicare. Kaplan-Meier and log-rank analyses were used for survival analysis. Logistic regression was used to assess factors associated with overall survival (OS). RESULTS: The USNETSG database included 2022 patients. Of those, 1425 were aged 18-64 years at index operation and were included in our analysis. Uninsured patients were more likely to have an emergent operation (7.9% versus 2.5%, p = 0.01) and less likely to receive postoperative somatostatin analog therapy (1.6% versus 9.9%, p = 0.03). OS at 1, 5, and 10 years was significantly higher for insured patients (96.3%, 88.2%, and 73.8%, respectively) than uninsured patients (87.7%, 71.9%, and 44.0%, respectively) (p < 0.01). On Cox multivariate regression analysis controlling for T/M stage, tumor grade, ASA class, and income level, being uninsured was independently associated with worse OS [hazard ratio (HR) 2.69, 95% confidence interval (CI) 1.32-5.48, p = 0.006]. CONCLUSIONS: Insurance status is an independent predictor of survival in patients with GEP-NETs. Our study highlights the importance of access to medical care, disparities related to insurance status, and the need to mitigate these disparities.

Treatment at Academic Centers Decreases Insurance-Based Survival Disparities in Colon Cancer.

BACKGROUND: Although insurance and race-based survival disparities in colon cancer are well studied, little is known regarding how these survival disparities are impacted by type of treating facility. MATERIALS AND METHODS: This is a retrospective cohort study of 433,997 patients diagnosed with colon adenocarcinoma using the National Cancer Database (NCDB). Using Cox proportional hazard analyses, we assessed overall survival (OS) as a function of race, insurance status, and treating facility, after adjusting for demographic and clinical factors. We also assessed differences in OS according to race and insurance status stratified by treating facility type. RESULTS: OS was significantly diminished for blacks (hazard ratio [HR], 1.09; 95% confidence interval [CI], 1.07-1.10; P < 0.001) and increased for patients of other race (primarily Asians; HR, 0.76; 95% CI, 0.74-0.78) compared with whites. Patients with private insurance had improved OS compared with uninsured (HR, 1.28; 95% CI, 1.25-1.31; P < 0.001), Medicaid (HR, 1.35; 95% CI, 1.33-1.38; P < 0.001) and Medicare (HR, 1.13, 95% CI, 1.12-1.15; P < 0.001) patients. Compared with patients treated at comprehensive community programs, patients treated at academic centers (ACs) had improved OS (HR, 0.86; 95% CI, 0.85-0.88; P < 0.001). When stratified by type of treating facility, racial disparities were not mitigated for patients treated at ACs compared with other facilities (P = 0.266 for interaction). At ACs, patients with Medicaid had persistent OS disparities compared with patients with private insurance (HR, 1.12; 95% CI, 1.09-1.15; P < 0.001), although these disparities were significantly diminished compared with patients treated at other facilities (HR, 1.41; 95% CI, 1.38-1.45; P < 0.001). CONCLUSIONS: Other race, private insurance, and treatment at AC were independently associated with improved OS in patients with colon cancer. Medicaid-based, but not race-based, survival disparities are reduced at ACs compared with other facilities.

Impact of perioperative blood transfusion on survival in pancreatic neuroendocrine tumor patients: analysis from the US Neuroendocrine Study Group.

BACKGROUND: Packed red blood cell (PRBC) transfusion has been associated with worse survival in multiple malignancies but its impact on pancreatic neuroendocrine tumors (PNETs) is unknown. The aim of this study was to determine the impact of PRBC transfusion on survival following PNET resection. METHODS: A retrospective cohort study of PNET patients was performed using the US Neuroendocrine Tumor Study Group database. Demographic and clinical factors were compared. Kaplan-Meier and log-rank analyses were performed. Factors associated with transfusion, overall (OS), recurrence-free (RFS) and progression-free survival (PFS) were assessed by logistic regression. RESULTS: Of 1129 patients with surgically resected PNETs, 156 (13.8%) received perioperative PRBC transfusion. Transfused patients had higher ASA Class, lower preoperative hemoglobin, larger tumors, more nodal involvement, and increased major complications (all p < 0.010). Transfused patients had worse median OS (116 vs 150 months, p < 0.001), worse RFS (83 vs 128 months, p < 0.01) in curatively resected (n = 1047), and worse PFS (11 vs 24 months, p = 0.110) in non-curatively resected (n = 82) patients. On multivariable analysis, transfusion was associated with worse OS (HR 1.80, p = 0.011) when controlling for TNM stage, tumor grade, final resection status, and pre-operative anemia. CONCLUSION: PRBC transfusion is associated with worse survival for patients undergoing PNET resection.

Sidedness of Colorectal Cancer Impacts Risk of Second Primary Gastrointestinal Malignancy.

INTRODUCTION: A history of colorectal cancer (CRC) increases the risk of subsequent gastrointestinal (GI) cancer. Cancers of the right colon, left colon, and rectum differ according to molecular profiles, responses to treatment, and outcomes. OBJECTIVE: The purpose of this study was to determine if CRC location is associated with differential risk for secondary primary GI malignancy. METHODS: A retrospective cohort of adults with CRC was compiled using the Surveillance, Epidemiology, and End Results database (1973-2015). Standardized incidence ratios (SIRs) for second primary GI malignancies were compared based on location of the index CRC (right colon, left colon, or rectum). RESULTS: The cohort included 281,413 adults with CRC (30.3% right, 35.3% left, 34.3% rectum). With a median 4.9-year follow-up, 12,064 (4.3%) patients developed a second primary GI malignancy (64% CRC, 36% non-CRC). Those with CRC at any location had higher than expected incidences of small intestine, bile duct, and other CRCs, and lower incidences of liver and gallbladder cancer. The SIR for small intestinal cancer was higher after right colon cancer than after left colon or rectal cancer. The esophageal cancer SIR was higher after left colon cancer. Pancreas cancer was higher than expected for right colon cancer, but lower for left colon and rectal cancer. CONCLUSION: The location of CRC leads to differences in the incidence and location of second primary GI malignancies and may be related to similarities in the associated carcinogenesis and molecular pathways or response to treatment. CRC location not only impacts treatment response and outcomes, but should also be considered during subsequent surveillance.

Comparative effectiveness of primary tumor resection in patients with stage IV colon cancer.

BACKGROUND: Although the safety of combination chemotherapy without primary tumor resection (PTR) in patients with stage IV colon cancer has been established, questions remain regarding a potential survival benefit with PTR. The objective of this study was to compare mortality rates in patients who had colon cancer with unresectable metastases who did and did not undergo PTR. METHODS: An observational cohort study was conducted among patients with unresectable metastatic colon cancer identified from the National Cancer Data Base (2003-2005). Multivariate Cox regression analyses with and without propensity score weighting (PSW) were performed to compare survival outcomes. Instrumental variable analysis, using the annual hospital-level PTR rate as the instrument, was used to account for treatment selection bias. To account for survivor treatment bias, in situations in which patients might die soon after diagnosis from different reasons, a landmark method was used. RESULTS: In the total cohort, 8641 of 15,154 patients (57%) underwent PTR, and 73.8% of those procedures (4972 of 6735) were at landmark. PTR was associated with a significant reduction in mortality using Cox regression (hazard ratio [HR], 0.45; 95% confidence interval [CI], 0.44-0.47) or PSW (HR, 0.46; 95% CI, 0. 44-0.49). However, instrumental variable analysis revealed a much smaller effect (relative mortality rate, 0.91; 95% CI, 0.87-0.96). Although a smaller benefit was observed with the landmark method using Cox regression (HR, 0.6; 95% CI, 0.55-0.64) and PSW (HR, 0.59; 95% CI, 0.54-0.64), instrumental variable analysis revealed no survival benefit (relative mortality rate, 0.97; 95% CI, 0.87-1.06). CONCLUSIONS: Among patients with unresectable metastatic colon cancer, after adjustment for confounder effects, PTR was not associated with improved survival compared with systemic chemotherapy; therefore, routine noncurative PTR is not recommended. Cancer 2017;123:1124-1133. © 2016 American Cancer Society.

Individualized Treatment Sequencing Selection Contributes to Optimized Survival in Patients with Rectal Cancer and Synchronous Liver Metastases.

BACKGROUND: The optimal treatment sequence for patients with advanced rectal cancer and synchronous resectable liver metastases is controversial. We examined the outcomes associated with an individualized selection of classic, reversed, or combined approaches. METHODS: Between 1999 and 2014, 268 patients with rectal cancer and synchronous liver-only metastases underwent curative-intent multimodality therapy. Demographics and tumor and treatment details were reviewed. Survival outcomes were examined across treatment sequences and time periods (1999-2003, 2004-2008, and 2009-2014). RESULTS: Overall, 150 (56.0%) patients underwent primary tumor resection first ('classic' approach), 44 (16.4%) patients underwent simultaneous resection of the primary and liver metastases ('combined' approach), and 74 (27.6%) patients underwent liver resection first ('reversed' approach). Patients who underwent the reversed approach had more liver metastases (3 [2-5]) at presentation (vs. 1 [1-2.5] in the combined approach or 1 [1-3] in the classic approach; p < 0.001). Over time (from 1999 to 2003, to 2009 to 2014), both patients undergoing curative-intent treatment (62-122 patients) and the relative proportion of patients undergoing the reversed approach (6.4-37.7%) significantly increased. Despite higher disease burden, the 5-year overall survival (OS) was higher for patients treated in 2009-2014 versus those treated in 1999-2003 (76% vs. 45%; p < 0.002). Two hundred and ten patients (78%) were rendered free of disease; however, 58 were not due to disease progression or treatment complications, and their 5-year OS was poor at 6%. CONCLUSIONS: Individualized selection of treatment sequence based on the liver metastases and primary tumor disease burden allowed most patients to complete resection of all gross disease, and is associated with a 5-year OS rate approaching that for stage III rectal cancer in the most recent era.

Effects of Flow and Bulk Vesicle Concentration on Supported Lipid Bilayer Formation.

Supported lipid bilayers (SLBs) have been used extensively in a variety of biotechnology applications and fundamental studies exploring lipid behavior. Despite their widespread use, various physicochemical parameters have yet to be thoroughly investigated for their impact on SLB formation. In this work, we have studied the importance of flow in inducing the rupture of surface adsorbed chicken egg-derived l-α-phosphatidylcholine (egg PC) vesicles on silica and gold surfaces via quartz crystal microbalance with dissipation monitoring (QCM-D). On silica at 25 °C, egg PC vesicles were found to adsorb in a flattened configuration (∼13 nm thick, compared to bulk vesicle diameters of ∼165 nm) but only undergo a transition to a stable SLB under flow conditions. In the absence of flow, an increase in system temperature to 37 °C was able to promote vesicle rupture and SLB formation on silica with a 10 times lower rupture time, compared to rupture under continuous flow (175 µL/min flow rate). Gold surfaces, with their increased hydrophobicity, led to less vesicle flattening once adsorbed (structures ∼60 nm thick), and did not support vesicle rupture or SLB formation, even at flow rates of up to 650 µL/min. We also showed that, under continuous flow conditions, vesicle adsorption rates on silica surfaces follow Langmuir kinetics, with an inverse dependence on bulk vesicle concentration, while an empirical power law dependence of vesicle rupture time on bulk vesicle concentration was observed. Ultimately, this work elicits fundamental insight into the importance of flow and bulk vesicle concentration in the adsorbed vesicle rupture process during SLB formation using QCM-D.

Comparing Faculty and Trainee Evaluators of First-Year Resident Skills.

OBJECTIVE: To determine if senior residents are comparable to faculty in assessing first-year resident skills on their overall assessment. BACKGROUND: As resident training moves towards a competency-based model, innovative approaches to evaluation and feedback through simulation need to be developed for both procedural as well as interpersonal and communication skills. In most areas of simulation, the faculty assess resident performance however; in clinical practice, first-year residents are often overseen and taught by senior residents. We aim to explore the agreement between faculty and senior resident assessors to determine if senior residents can be incorporated into a competency-based curriculum as appropriate evaluators of first-year resident skills. DESIGN: Annual surgical first year resident training for central line placement, obtaining informed consent and breaking bad news at a single institution is assessed through an overall assessment (OA). In previous years, only faculty have been the evaluators for the OA. In this study, select senior residents were asked to participate as evaluators and agreement between groups of evaluators was assessed across the 3 tasks taught during surgical first-year resident training. SETTING: Vanderbilt University Medical Center, tertiary hospital, Simulation Center. PARTICIPANTS: Anesthesia and surgery interns, chief residents, anesthesia and surgical faculty. RESULTS: Agreement between faculty and senior resident assessors was strongest for the central line placement simulation with a faculty average competency score of 10.71 and 9.59 from senior residents (κ = 0.43; 95% CI: -0.2, 0.34). Agreement was less substantial for simulated informed consent (κ = 0.08; 95% CI: -0.19, 0.36) and the breaking bad news simulation (κ = 0.07; 95% CI: -0.2, 0.34). CONCLUSION: Select senior residents are comparable to faculty evaluators for procedural competency; however, there was less agreement between evaluator groups for interpersonal and communication-based competencies.