Initial Experience With Single-Port Robotic Right Colectomies: Results of an Investigator-Initiated Investigational Device Exemption Study Using a Novel Single-Port Robotic Platform.

BACKGROUND: Minimally invasive surgical techniques have been widely adopted in colorectal surgery. New technological breakthroughs have led to even less invasive alternatives like single-port surgery, but this has been hindered by technical challenges such as the collision of robotic arms within a limited space. The Intuitive da Vinci Single-Port robotic platform is a novel system that overcomes some of these challenges. IMPACT OF INNOVATION: This study aimed to assess the safety and feasibility of the Intuitive da Vinci Single-Port robotic platform in right segmental colectomies among adult patients. These findings may set the stage for more widespread use of single-port robotic surgery. TECHNOLOGY, MATERIALS, AND METHODS: The Intuitive da Vinci Single-Port robot is a system designed specifically for single-port robotic surgery. This platform enables flexible port location and efficient internal and external range of motion using a single C-shaped arm. In the present study, right colectomies were performed in adult patients using this platform between May 2022 and November 2022, and they were compared to right colectomies in adult patients performed using the standard multiport platform between January 2019 and December 2022. The main outcome measure was safety and quality event rates. PRELIMINARY RESULTS: Of 30 patients, 16.7% of patients (n = 5) underwent single-port robotic right colectomy and 83.3% (n = 25) underwent multiport right colectomy. In the single-port group, 40% of patients (n = 2) developed a safety/quality event (postoperative portal vein thrombosis and excessive postoperative pain). In the multiport group, 32% of patients (n = 8) developed 1 safety/quality event and 8% (n = 2) had more than 1 event. CONCLUSIONS AND FUTURE DIRECTIONS: This preliminary study, one of the first Food and Drug Administration-approved, investigator-initiated uses of this platform in colorectal surgeries, shows that this platform is a safe and feasible option for right colectomies. On preliminary evaluation, it appears comparable in terms of relevant safety/quality events to the multiport platform. CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov NCT05321134.

Electronic Surgical Consent Delivery Via Patient Portal to Improve Perioperative Efficiency.

Importance: Many health systems use electronic consent (eConsent) for surgery, but few have used surgical consent functionality in the patient portal (PP). Incorporating the PP into the consent process could potentially improve efficiency by letting patients independently review and sign their eConsent before the day of surgery. Objective: To evaluate the association of eConsent delivery via the PP with operational efficiency and patient engagement. Design, Setting, and Participants: This mixed-methods study consisted of a retrospective quantitative analysis (February 8 to August 8, 2023) and a qualitative analysis of semistructured patient interviews (December 1, 2023, to January 31, 2024) of adult surgical patients in a health system that implemented surgical eConsent. Statistical analysis was performed between September 1, 2023, and June 6, 2024. Main Outcomes and Measures: Patient demographics, efficiency metrics (first-start case delays), and PP access logs were analyzed from electronic health records. Qualitative outcomes included thematic analysis from semistructured patient interviews. Results: In the PP-eligible cohort of 7672 unique patients, 8478 surgical eConsents were generated (median [IQR] age, 58 [43-70] years; 4611 [54.4%] women), of which 5318 (62.7%) were signed on hospital iPads and 3160 (37.3%) through the PP. For all adult patients who signed an eConsent using the PP, patients waited a median (IQR) of 105 (17-528) minutes to view their eConsent after it was electronically pushed to their PP. eConsents signed on the same day of surgery were associated with more first-start delays (odds ratio, 1.59; 95% CI, 1.37-1.83; P < .001). Themes that emerged from patient interviews included having a favorable experience with the PP, openness to eConsent, skimming the consent form, and the importance of the discussion with the surgeon. Conclusions and Relevance: These findings suggest that eConsent incorporating PP functionality may reduce surgical delays and staff burden by allowing patients to review and sign before the day of surgery. Most patients spent minimal time engaging with their consent form, emphasizing the importance of surgeon-patient trust and an informed consent discussion. Additional studies are needed to understand patient perceptions of eConsent, PP, and barriers to increased uptake.

The Effect of Intersectionality on Attrition among US General Surgery Trainees.

OBJECTIVE: To examine the association between intersectionality of race, ethnicity, and sex on retention of U.S. general surgery residents. SUMMARY BACKGROUND DATA: There are limited data on the role that intersectionality plays on the US general surgery resident experience. METHODS: Analysis was performed using Association of American Medical Colleges (AAMC) data for general surgery residents who started their training between 2005-2015 (followed through completion). Regression analyses were used to assess demographic associations with time to attrition or successful completion of residency training. Associations between faculty and resident demographics were assessed. RESULTS: 25,029 residents were included. Over the decade-long study period, the number of underrepresented in medicine (UIM) residents as a percentage of all residents remained similar from 17% to 19% (P=0.24). The percent of UIM males starting training in 2005 was 11% and 12% in 2015 (P-value=0.38). UIM females comprised 5.5% of trainees in 2005 and increased to 6.9% (P-value=0.003) in 2015; and female non-UIM residents increased from 23 to 28% (P-value<0.001). The overall rate of resident attrition was 15%. UIM females had the highest yearly attrition rate at 21% compared to non-UIM males at 13% (HR 1.7, P<0.001). UIM females were more likely to leave residency compared to UIM males (HR: 1.5; P<0.001). The percent of UIM faculty was positively correlated with percent of UIM residents (r=0.64, P<0.001). CONCLUSIONS: Increasing intersectionality is positively associated with attrition during surgery residency. The diversity of faculty appears to be associated with resident diversity.

Surgeon Intersectionality and Academic Promotion and Retention in the US.

Introduction: Efforts have been made to increase the number of women and physicians who are underrepresented in medicine (UIM). However, surgery has been slow to diversify, and there are limited data surrounding the impact of intersectionality. Objective: To assess the combined association of race and ethnicity and sex with rates of promotion and attrition among US academic medical department of surgery faculty. Design, Setting, and Participants: This was a retrospective cohort study using faculty roster data from the Association of American Medical Colleges. All full-time academic department of surgery faculty with an appointment any time from January 1, 2005, to December 31, 2020, were included. Study data were analyzed from September 2022 to February 2023. Exposures: Full-time academic faculty in a department of surgery with a documented self-reported race, ethnicity, and sex within the designated categories of the faculty roster of Association of American Medical Colleges. Main Outcomes and Measures: Trends in race and ethnicity and sex, rates of promotion, and rates attrition from 2010 to 2020 were assessed with Kaplan-Meier and Cox time-to-event analyses. Results: A total of 31 045 faculty members (23 092 male [74%]; 7953 female [26%]) from 138 institutions were included. The mean (SD) program percentage of UIM male faculty increased from 8.4% (5.5%) in 2010 to 8.5% (6.2%) in 2020 (P < .001), whereas UIM female faculty members increased from 2.3% (2.6%) to 3.3% (2.5%) over the 10-year period (P < .001). The mean program percentage of non-UIM females increased at every rank (percentage point increase per year from 2010 to 2020 in instructor: 1.1; 95% CI, 0.73-1.5; assistant professor: 1.1; 95% CI, 0.93-1.3; associate professor: 0.55; 95% CI, 0.49-0.61; professor: 0.50; 95% CI, 0.41-0.60; all P < .001). There was no change in the mean program percentage of UIM female instructors or full professors. The mean (SD) percentage of UIM female assistant and associate professors increased from 3.0% (4.1%) to 5.0% (4.0%) and 1.6% (3.2%) to 2.2% (3.4%), respectively (P =.002). There was no change in the mean program percentage of UIM male instructors, associate, or full professors. Compared with non-Hispanic White males, Hispanic females were 32% less likely to be promoted within 10 years (hazard ratio [HR], 0.68; 95% CI, 0.54-0.86; P <.001), non-Hispanic White females were 25% less likely (HR, 0.75; 95% CI, 0.71-0.78; P <.001), Hispanic males were 15% less likely (HR, 0.85; 95% CI, 0.76-0.96; P =.007), and Asian females were 12% less likely (HR, 0.88; 95% CI, 0.80-0.96; P =.03). Non-UIM males had the shortest median (IQR) time to promotion, whereas non-UIM females had the longest (6.9 [6.8-7.0] years vs 7.2 [7.0-7.6] years, respectively; P < .001). After 10 years, 79% of non-UIM males (13 202 of 16 299), 71% of non-UIM females (3784 of 5330), 68% of UIM males (1738 of 2538), and 63% of UIM females (625 of 999) remained on the faculty. UIM females had a higher risk of attrition compared with non-UIM females (HR, 1.3; 95% CI, 1.1-1.5; P = .001) and UIM males (HR, 1.2; 95% CI, 1.0-1.4; P = .05). The mean (SE) time to attrition was shortest for UIM females and longest for non-UIM males (8.2 [0.14] years vs 9.0 [0.02] years, respectively; P < .001). Conclusion and Relevance: Results of this cohort study suggest that intersectionality was associated with promotion and attrition, with UIM females least likely to be promoted and at highest risk for attrition. Further efforts to understand these vulnerabilities are essential.

Factors associated with trauma recidivism in young children.

BACKGROUND: Trauma recidivism is associated with future trauma-associated morbidity and mortality. Previous evidence suggests that socioeconomic factors predict trauma recidivism in older children (10-18 years); however, risk factors in US children 10 years and younger have not been studied. We sought to determine the factors associated with trauma recidivism in young children 10 years and younger. METHODS: We conducted a retrospective cohort study of pediatric trauma patients 10 years and younger who presented to a single American College of Surgeons-verified Level I pediatric trauma center from July 1, 2017, to June 30, 2021. All patients were evaluated for prior injury during trauma registry entry. Characteristics at the index injury were collected via chart review. Patients were geocoded to assess Social Vulnerability Index. Logistic regression examined factors associated with recidivism. Best subset selection was used to compare multivariable models and identify the most predictive and parsimonious model. Statistical significance was set at p < 0.05. RESULTS: Of the 3,518 patients who presented in the study period, 169 (4.8%) experienced a prior injury. Seventy-six percent (n = 128) had one prior injury presentation, 18% (n = 31) had two prior presentations, and 5.9% (n = 10) had three or more. Falls were the most common mechanism in recidivists (63% vs. 52%, p = 0.009). Child physical abuse occurred in 6.5% of patients, and 0.9% experienced penetrating injury. The majority (n = 137 [83%]) were discharged home from the emergency department. There was no significant difference in the frequency of penetrating injury and child physical abuse between recidivists and nonrecidivists. Following logistic regression, the most parsimonious model demonstrated that recidivism was associated with comorbidities, age, falls, injury location, nontransfer, and racialization. No significant associations were found with Social Vulnerability Index and insurance status. CONCLUSION: Medical comorbidities, young age, injury location, and falls were primarily associated with trauma recidivism. Support for parents of young children and those with special health care needs through injury prevention programs could reduce trauma recidivism in this population. LEVEL OF EVIDENCE: Prognostic and Epidemiological; Level III.

The impact of histologic subtype on primary site surgery in the management of metastatic lobular versus ductal breast cancer: a population based study from the National Cancer Database (NCDB).

PURPOSE: Primary site surgery for metastatic breast cancer improves local control but does not impact overall survival. Whether histologic subtype influences patient selection for surgery is unknown. Given differences in surgical management between early-stage lobular versus ductal disease, we evaluated the impact of histology on primary site surgery in patients with metastatic breast cancer. METHODS: The National Cancer Database (NCDB, 2010-2016) was queried for patients with stage IV HR-positive, HER2-negative invasive lobular carcinoma (ILC) and invasive ductal carcinoma (IDC). We compared clinicopathologic features, primary site surgery rates, and outcomes by histologic subtype. Multivariable Cox proportional hazard models with and without propensity score matching were used for overall survival (OS) analyses. RESULTS: In 25,294 patients, primary site surgery was slightly but significantly less common in the 6,123 patients with ILC compared to the 19,171 patients with IDC (26.9% versus 28.8%, p = 0.004). Those with ILC were less likely to receive chemotherapy (41.3% versus 47.4%, p < 0.0001) or radiotherapy (29.1% versus 37.9%, p < 0.0001), and had shorter OS. While mastectomy rates were similar, those with ILC who underwent lumpectomy had significantly higher positive margin rates (ILC 15.7% versus IDC 11.2%, p = 0.025). In both groups, the odds of undergoing surgery decreased over time, and were higher in younger patients with T2/T3 tumors and higher nodal burden. CONCLUSION: Lobular histology is associated with less primary site surgery, higher positive margin rates, less radiotherapy and chemotherapy, and shorter OS compared to those with HR-positive HER2-negative IDC. These findings support the need for ILC-specific data and treatment approaches in the setting of metastatic disease.

Association of body mass index with post-liver transplant outcomes.

BACKGROUND: Patients with obesity have inferior outcomes after general surgery procedures, but studies evaluating post-liver transplant (LT) outcomes have been limited by small sample sizes or lack of granularity of outcomes. We evaluated the relationship between obesity and post-LT outcomes, including those observed in other populations to be obesity-related. METHODS: Included were 1357 LT recipients prospectively enrolled in the ambulatory pre-LT setting at 8 U.S. CENTERS: Recipient were categorized by body mass index (BMI, kg/m2 ): non-obese (BMI < 30), class 1 obesity (BMI 30-<35), and classes 2-3 obesity (BMI ≥ 35). Post-transplant complications were compared by BMI using Chi-square and rank-sum testing, logistic regression, Kaplan-Meier curves, and Cox regression. RESULTS: Classes 2-3 obesity was associated with higher adjusted odds than non-obesity of venous thrombosis [adjusted odds ratio (aOR) 2.06, 95% CI 1.01-4.23, p = .047] and wound dehiscence (aOR 2.45, 95% CI 1.19-5.06, p = .02). Compared with non-obese recipients, post-LT hospital stay was significantly longer for recipients with classes 2-3 obesity [p = .01; median (Q1-Q3) 9 (6-14) vs. 8 (6-12) days) or class 1 obesity [p = .002; 9 (6-14) vs. 8 (6-11) days].  Likelihood of ICU readmission, infection, discharge to a non-home facility, rejection, 30-day readmission, and 1-year readmission were similar across BMI categories (all p > .05). CONCLUSION: Compared to non-obese recipients, obese recipients had similar post-LT survival but longer hospital stay and higher likelihood of wound dehiscence and venous thrombosis. These findings underscore that obesity alone should not preclude LT, but recipients with obesity should be monitored for obesity-related complications such as wound dehiscence and venous thrombosis.

The liver frailty index is a predictor of healthcare utilization after liver transplantation in older adults.

BACKGROUND: Older adults have higher healthcare utilization after liver transplantation (LT), yet objective risk stratification tools in this population are lacking. We evaluated the Liver Frailty Index (LFI) as one potential tool. METHODS: Ambulatory LT candidates ≥65 years without hepatocellular carcinoma (HCC) who underwent LT from 1/2012 to 6/2022 at 8 U.S. centers were included. Estimates of the difference in median using quantile regression were used to assess the adjusted association between LFI and hospitalized days within 90 days post-LT. RESULTS: Of 131 LT recipients, median (interquartile range [IQR]) (1st -3rd quartiles) age was 68 years (66-70); median pre-LT MELD-Na was 19 (15-24). Median LFI was 4.1 (3.6-4.7); 27% were frail (LFI≥4.5). Median hospitalized days within 90 days post-LT was 11 (7-20). Compared with non-frail patients, frail patients were hospitalized for a median of 5 days longer post-LT (95% CI .30-9.7, p = .04). Each .5 unit increase in pre-LT LFI was associated with an increase of 1.16 days (95%CI .42-2.69, p = .02) in hospitalized days post-LT. CONCLUSION: Among older adults undergoing LT, frailty was associated with more hospitalized days within 90 days after LT. The LFI can identify older adults who might benefit from pre-LT or early post-LT programs which may reduce post-LT healthcare utilization, such as early rehabilitation or post-hospital discharge programs.

Clinical Characteristics Associated With Posttransplant Survival Among Adults 70 Years Old or Older Undergoing Liver Transplantation.

GOALS: We sought to identify pre-liver transplantation (LT) characteristics among older adults associated with post-LT survival. BACKGROUND: The proportion of older patients undergoing deceased-donor liver transplantation (DDLT) has increased over time. STUDY: We analyzed adult DDLT recipients in the United Network for Organ Sharing registry from 2016 through 2020, excluding patients listed as status 1 or with a model of end-stage liver disease exceptions for hepatocellular carcinoma. Kaplan-Meier methods were used to estimate post-LT survival probabilities among older recipients (age ≥70 y). Associations between clinical covariates and post-LT mortality were assessed using Cox regressions. RESULTS: Of 22,862 DDLT recipients, 897 (4%) were 70 years old or older. Compared with younger recipients, older recipients had worse overall survival ( P < 0.01) (1 y: 88% vs 92%, 3 y: 77% vs 86%, and 5 y: 67% vs 78%). Among older adults, in univariate Cox regressions, dialysis [hazards ratio (HR): 1.96, 95% CI: 1.38-2.77] and poor functional status [defined as Karnofsky Performance Score (KPS) <40] (HR: 1.82, 95% CI: 1.31-2.53) were each associated with mortality, remaining significant on multivariable Cox regressions. The effect of dialysis and KPS <40 at LT on post-LT survival (HR: 2.67, 95% CI: 1.77-4.01) was worse than the effects of either KPS <40 (HR: 1.52, 95% CI: 1.03-2.23) or dialysis alone (HR: 1.44, 95% CI: 0.62-3.36). Older recipients with KPS >40 without dialysis had comparable survival rates compared with younger recipients ( P = 0.30). CONCLUSIONS: While older DDLT recipients had worse overall post-LT survival compared with younger recipients, favorable survival rates were observed among older adults who did not require dialysis and had poor functional status. Poor functional status and dialysis at LT may be useful to stratify older adults at higher risk for poor post-LT outcomes.

AFP-L3 and DCP strongly predict early hepatocellular carcinoma recurrence after liver transplantation.

BACKGROUND & AIMS: Alpha-fetoprotein (AFP) predicts hepatocellular carcinoma (HCC) recurrence after liver transplant (LT) but remains an imperfect biomarker. The role of DCP (des-gamma-carboxyprothrombin) and AFP-L3 (AFP bound to Lens culinaris agglutinin) in predicting HCC recurrence remains incompletely characterized. AFP-L3 and DCP could identify patients at high risk of post-transplant HCC recurrence and serve as liver transplant exclusion criteria to defer transplant until patients receive additional risk-reducing pre-transplant locoregional therapy. METHODS: This prospective cohort study included consecutive patients with HCC who underwent LT (within or down-staged to Milan criteria) between 2017 and 2022. Pre-transplant AFP, AFP-L3, and DCP measurements were obtained. The primary endpoint was the ability of biomarkers to predict HCC recurrence-free survival. RESULTS: This cohort included 285 patients with a median age of 67 (IQR 63-71). At LT, median biomarker values were AFP 5.0 ng/ml (IQR 3.0-12.1), AFP-L3 6.7% (0.5-13.2), and DCP 1.0 ng/ml (0.3-2.8). Most (94.7%) patients received pre-LT locoregional therapy. After a median post-LT follow-up of 3.1 years, HCC recurrence was observed in 18 (6.3%) patients. AFP-L3 and DCP outperformed AFP with C-statistics of 0.81 and 0.86 respectively, compared with 0.74 for AFP. A dual-biomarker combination of AFP-L3 ≥15% and DCP ≥7.5 predicted 61.1% of HCC recurrences, whereas HCC only recurred in 7 of 265 (2.6%) patients not meeting this threshold. The Kaplan-Meier recurrence-free survival rate at 3 years post-LT was 43.7% for patients with dual-positive biomarkers compared to 97.0% for all others (p <0.001). CONCLUSIONS: Dual-positivity for AFP-L3 ≥15% and DCP ≥7.5 strongly predicted post-LT HCC recurrence. This model could refine LT selection criteria and identify high-risk patients who require additional locoregional therapy prior to LT. IMPACT AND IMPLICATIONS: Alpha-fetoprotein (AFP) is used to predict hepatocellular carcinoma (HCC) recurrence after liver transplant, but it remains an imperfect biomarker. In this prospective study, the biomarkers DCP (des-gamma-carboxyprothrombin) and AFP-L3 (AFP bound to Lens culinaris agglutinin) strongly predicted early HCC recurrence and outperformed AFP. A dual-biomarker combination of AFP-L3 ≥15% and DCP ≥7.5 predicted the majority of recurrences and could be used to further refine liver transplant eligibility criteria.

The impact of histologic subtype on primary site surgery in the management of metastatic lobular versus ductal breast cancer: a population based study from the National Cancer Database.

Purpose: Primary site surgery for metastatic breast cancer improves local control but does not impact overall survival. Whether histologic subtype influences patient selection for surgery is unknown. Given differences in surgical management between early-stage lobular versus ductal disease, we evaluated the impact of histology on primary site surgery in patients with metastatic breast cancer. Methods: The National Cancer Database (NCDB, 2010-2016) was queried for patients with stage IV HR-positive, HER2-negative invasive lobular carcinoma (ILC) and invasive ductal carcinoma (IDC). We compared clinicopathologic features, primary site surgery rates, and outcomes by histologic subtype. Multivariable Cox proportional hazard models with and without propensity score matching were used for overall survival (OS) analyses. Results: In 25,294 patients, primary site surgery was slightly but significantly less common in the 6,123 patients with ILC compared to the 19,171 patients with IDC (26.9% versus 28.8%, p = 0.004). Those with ILC were less likely to receive chemotherapy (41.3% versus 47.4%, p < 0.0001) or radiotherapy (29.1% versus 37.9%, p < 0.0001), and had shorter OS. While mastectomy rates were similar, those with ILC had more positive margins (10.6% versus 8.3%, p = 0.005). In both groups, the odds of undergoing surgery decreased over time, and were higher in younger patients with T2/T3 tumors and higher nodal burden. Conclusion: Lobular histology is associated with less primary site surgery, higher positive margin rates, less radiotherapy and chemotherapy, and shorter OS compared to those with HR-positive HER2-negative IDC. These findings support the need for ILC-specific data and treatment approaches in the setting of metastatic disease.

Interrater reliability of chart-based assessment of functional impairment after pediatric injury using the functional status scale.

BACKGROUND: Functional impairment has been proposed as an alternative outcome for quality improvement in pediatric trauma. The functional status scale (FSS) has been used in studies of injured children, but has only been validated with resource-intensive in-person assessment. Implementation with retrospective chart-based FSS assessment would offer a simplified and scalable alternative. The purpose of this study was to evaluate interrater reliability of retrospective FSS assessment and to identify factors associated with unreliable assessment. METHODS: A retrospective cohort of admissions to a Level I pediatric trauma center between July 2020 and June 2021 was analyzed. Two physicians and two nurse registrars reviewed charts to obtain measures of six FSS domains (mental status, sensory functioning, communication, motor functioning, feeding, and respiratory status) at discharge. Functional impairment was categorized by total FSS scores as good (6,7), mild impairment (8,9), moderate impairment (10-15), severe impairment (16-21), or very severe impairment (>21). Interrater reliability was assessed using intraclass correlation (ICC). Predictors of rater disagreement were evaluated using multivariable logistic regression. RESULTS: The cohort included 443 children with a mean age of 7.4 years (standard deviation, 5.4 years) and median Injury Severity Score of 9 (interquartile range, 5-12). The median time per chart to assess FSS was 2 minutes (interquartile range, 1-2). Thirty-seven patients (8%) had functional impairment at discharge. Interrater reliability was excellent for total FSS score (ICC = 0.87) and good for FSS impairment categorization (ICC = 0.80). Rater disagreement of functional impairment categorization occurred in 14% of cases overall. Higher level of functional impairment and use of therapies (occupational and speech language therapy) were independently associated with more frequent rater disagreement. CONCLUSION: Chart-based FSS assessment is feasible and reliable, but may require more detailed review for patients with higher level of impairment that require allied health therapy. Validation of chart-based assessment is needed before widespread implementation. LEVEL OF EVIDENCE: Prognostic/Epidemiological, Level III.

Serum and plasma protein biomarkers associated with frailty in patients with cirrhosis.

Frailty, a clinical phenotype of decreased physiological reserve, is a strong determinant of adverse health outcomes in patients with cirrhosis. The only cirrhosis-specific frailty metric is the Liver Frailty Index (LFI), which must be administered in person and may not be feasible for every clinical scenario. We sought to discover candidate serum/plasma protein biomarkers that could differentiate frail from robust patients with cirrhosis. A total of 140 adults with cirrhosis awaiting liver transplantation in the ambulatory setting with LFI assessments and available serum/plasma samples were included. We selected 70 pairs of patients on opposite ends of the frailty spectrum (LFI>4.4 for frail and LFI<3.2 for robust) who were matched by age, sex, etiology, HCC, and Model for End-Stage Liver Disease-Sodium. Twenty-five biomarkers with biologically plausible associations with frailty were analyzed using ELISA by a single laboratory. Conditional logistic regression was used to examine their association with frailty. Of the 25 biomarkers analyzed, we identified 7 proteins that were differentially expressed between frail and robust patients. We observed differences in 6 of the 7 proteins in the expected direction: (a) higher median values in frail versus robust with growth differentiation factor-15 (3682 vs. 2249 pg/mL), IL-6 (17.4 vs. 6.4 pg/mL), TNF-alpha receptor 1 (2062 vs. 1627 pg/mL), leucine-rich alpha-2 glycoprotein (44.0 vs. 38.6 µg/mL), and myostatin (4066 vs. 6006 ng/mL) and (b) lower median values in frail versus robust with alpha-2-Heremans-Schmid glycoprotein (0.11 vs. 0.13 mg/mL) and free total testosterone (1.2 vs. 2.4 ng/mL). These biomarkers represent inflammatory, musculoskeletal, and endocrine/metabolic systems, reflecting the multiple physiological derangements observed in frailty. These data lay the foundation for confirmatory work and development of a laboratory frailty index for patients with cirrhosis to improve diagnosis and prognostication.

Number of Local Regional Therapies for Hepatocellular Carcinoma and Peri-Operative Outcomes after Liver Transplantation.

The wait times for patients with hepatocellular carcinoma (HCC) listed for liver transplant are longer than ever, which has led to an increased reliance on the use of pre-operative LRTs. The impact that multiple rounds of LRTs have on peri-operative outcomes following transplant is unknown. This was a retrospective single center analysis of 298 consecutive patients with HCC who underwent liver transplant (January 2017 to May 2021). The data was obtained from two institution-specific databases and the TransQIP database. Of the 298 patients, 27 (9.1%) underwent no LRTs, 156 (52.4%) underwent 1-2 LRTs, and 115 (38.6%) underwent ≥3 LRTs prior to LT. The patients with ≥3 LRTs had a significantly higher rate of bile leak compared to patients who received 1-2 LRTs (7.0 vs. 1.3%, p = 0.014). Unadjusted and adjusted regression analyses demonstrated a significant association between the total number of LRTs administered and bile leak, but not rates of overall biliary complications. The total number of LRTs was not significantly associated with any other peri-operative or post-operative outcome measure. These findings support the aggressive use of LRTs to control HCC in patients awaiting liver transplant, with further evaluation needed to confirm the biliary leak findings.

Association of Frailty With Health-Related Quality of Life in Liver Transplant Recipients.

Importance: Frailty has been recognized as a risk factor for mortality after liver transplant (LT) but little is known of its association with functional status and health-related quality of life (HRQL), termed global functional health, in LT recipients. Objective: To evaluate the association between pre-LT and post-LT frailty with post-LT global functional health. Design, Setting, and Participants: This prospective cohort study was conducted at 8 US LT centers and included adults who underwent LT from October 2016 to February 2020. Exposures: Frail was defined by a pre-LT Liver Frailty Index (LFI) score of 4.5 or greater. Main Outcomes and Measures: Global functional health at 1 year after LT, assessed using surveys (Short Form-36 [SF-36; summarized by physical component scores (PFC) and mental component summary scores (MCS)], Instrumental Activities of Daily Living scale) and performance-based tests (LFI, Fried Frailty Phenotype, and Short Physical Performance Battery). Results: Of 358 LT recipients (median [IQR] age, 60 [53-65] years; 115 women [32%]; 25 [7%] Asian/Pacific Islander, 21 [6%] Black, 54 [15%] Hispanic White, and 243 [68%] non-Hispanic White individuals), 68 (19%) had frailty pre-LT. At 1 year post-LT, the median (IQR) PCS was lower in recipients who had frailty vs those without frailty pre-LT (42 [31-53] vs 50 [38-56]; P = .002), but the median MCS was similar. In multivariable regression, pre-LT frailty was associated with a -5.3-unit lower post-LT PCS (P < .001), but not MCS. The proportion who had difficulty with 1 or more Instrumental Activities of Daily Living (21% vs 10%) or who were unemployed/receiving disability (38% vs 29%) was higher in recipients with vs without frailty. In a subgroup of 210 recipients with LFI assessments 1 year post-LT, 13% had frailty at 1 year post-LT. Recipients who had frailty post-LT reported lower adjusted SF-36-PCS scores (coefficient, -11.4; P < .001) but not SF-36-MCS scores. Recipients of LT who had frailty vs those without frailty 1 year post-LT also had worse median (IQR) Fried Frailty Phenotype scores (1 [1-2] vs 1 [0-1]) and higher rates of functional impairment by a Short Physical Performance Battery of 9 or less (42% vs 20%; P = .01). Conclusions and Relevance: In this cohort study, pre-LT frailty was associated with worse global functional health 1 year after LT. The presence of frailty after LT was also associated with worse HRQL in physical, but not mental, subdomains. These data suggest that interventions and therapeutics that target frailty that are administered before and/or early post-LT may help to improve the health and well-being of LT recipients.

Disease-Specific Survival Trends for Patients Presenting with Differentiated Thyroid Cancer and Distant Metastases in the United States, 1992-2018.

Objective: Differentiated thyroid cancer (DTC) is associated with an excellent prognosis, but patients with distant metastatic DTC have a 10-year disease-specific survival (DSS) of just 50%. The incidence of distant metastatic DTC has steadily increased in the United States since the 1980s. The aim of this study was to examine trends in survival and treatment for patients with distant metastatic DTC. Methods: In this population-based, retrospective cohort study, patients with distant metastatic DTC were identified from the Surveillance, Epidemiology, and End Results-13 cancer registry program. Multivariable logistic and Cox regression analyses were used to examine factors associated with DSS and management. Annual percentage changes in treatment patterns were calculated using log-linear regression. Results: During 1992-2018, 1991 patients (69.7% white, 58.0% female, 47.5% aged ≥65 years) were diagnosed with distant metastatic DTC. Papillary thyroid cancer was the most common histological type (74.5%). While the 10-year DSS for overall DTC increased over time (95.4% for patients diagnosed in 1992-1998, 96.6% in 1999-2008, and 97.3% in 2009-2018; p < 0.01), 10-year DSS for DTC with distant metastases did not change (50.2%, 47.3%, and 52.4%, respectively; p = 0.48). Ten-year DSS rates were reduced for patients aged ≥65 years (28.1%), patients undergoing nonsurgical treatment with external beam radiation therapy and/or systemic therapy (6.0%), and patients undergoing no/unknown treatment (32.8%). On multivariable analysis, oncocytic carcinoma, age 65-79 and ≥80 years, male sex, node-positive disease, larger tumor size, nonsurgical treatment, and no/unknown treatment were associated with increased risk of thyroid cancer death. Between 1992 and 2018, the rate of nonsurgical treatment increased, on average, 1.3% per year (1992-1998: 22.9% vs. 2009-2018: 25.6%; p = 0.03), and the rate of patients receiving no/unknown treatment increased 1.9% per year (1992-1998: 11.3% vs. 2009-2018: 15.6%; p = 0.01). Patients aged 65-79 and ≥80 years were more likely than younger patients to receive nonsurgical management or no/unknown treatment. Conclusion: Patients diagnosed with distant metastatic DTC have experienced no improvement in DSS over the past three decades. An increasing proportion of patients diagnosed with distant metastatic DTC are receiving nonsurgical treatment or no/unknown treatment over time; the proportion was highest among the oldest patients.

Radiation Modality (Proton/Photon), Timing, and Complication Rates in Patients With Breast Cancer Receiving 2-Stages Expander/Implant Reconstruction.

PURPOSE: Our purpose is to explore the effect of postmastectomy radiation therapy (PMRT) modality and timing on complication rates in breast cancer patients receiving immediate 2-stages expander/implant. METHODS AND MATERIALS: We reviewed the charts of 661 patients who underwent immediate 2-stages expander/implant with/without PMRT at our institution from 2000 to 2019. Patients were divided into 3 cohorts: no radiation, PMRT to expanders (RTE), and PMRT to implants after expander exchange (RTI). PMRT was delivered either with 3-dimensional conformal photon with or without chest wall boost (CWB) or proton therapy. Reconstruction complications were defined as infection/necrosis requiring debridement, capsular-contracture requiring capsulotomy, and reconstruction failure requiring prothesis removal. Logistic regression and Cox models were used to assess the effect of different radiation therapy modalities on complication rates and local control. RESULTS: Among 661 patients, 309 (46.7%) received PMRT, 220 of the 309 (71.2%) received RTE before exchange, and 89 (28.8%) received RTI after exchange. Seventeen out of 309 (5.5%) patients received proton therapy. The complications among RTE versus RTI cohorts were 22.7% versus 15.7% for infection/necrosis, 13.6% versus 19.1% for capsular-contracture, and 39.5% versus 31.5% for overall reconstruction failure, respectively. Among proton patients, 8/17 (47%) developed capsular contracture compared with 16.4% (24/146) and 10.3% (15/146) in CWB and non-CWB groups, respectively. Adjusted multivariable analysis showed no significant difference between RTI and RTE in terms of infection/necrosis and capsular contracture. Yet, RTE significantly increased overall reconstruction failure compared with RTI (39.5% vs 31.5%; odds ratio [OR], 2.11; P = .02). Protons significantly increased capsular contracture compared with both CWB and non-CWB groups (OR, 5.4; P = .01 and OR, 10.9; P < .001, respectively). Moreover, proton significantly increased overall reconstruction failure. The 5-year local control rates were 95.3% and 97.7% for RTE and RTI, respectively (hazard ratio, 1.2; P = .7). CONCLUSIONS: Early radiation to the expander before the exchange to implant significantly increased overall reconstruction failure without improving local control. Protons significantly increased capsular contracture rates and overall reconstruction failure leading to more revision surgeries.

The 21-Gene Recurrence Score in Clinically High-Risk Lobular and Ductal Breast Cancer: A National Cancer Database Study.

OBJECTIVE: The aim of this study was to evaluate whether patients with invasive lobular carcinoma (ILC) are more likely to have discordant clinical and genomic risk than those with invasive ductal carcinoma (IDC) when using the 21-gene recurrence score (RS), and to assess overall survival outcomes of patients with 1-3 positive nodes and RS ≤25 with and without chemotherapy, stratified by histology. METHODS: We performed a cohort study using the National Cancer Database and included patients with hormone receptor-positive, HER2-negative, stage I-III invasive breast cancer who underwent 21-gene RS testing. Our primary outcome was rate of discordant clinical and genomic risk status by histologic subtype. Propensity score matching was used to compare 60-month overall survival in individuals with 1-3 positive nodes and RS ≤25 who did and did not receive chemotherapy. RESULTS: Overall, 186,867 patients were included in our analysis, including 37,685 (20.2%) patients with ILC. There was a significantly higher rate of discordant clinical and genomic risk in patients with ILC compared with IDC. Among patients with 1-3 positive nodes and RS ≤25, there was no significant difference in survival between those who did and did not receive chemotherapy in the IDC or ILC cohorts. Unadjusted exploratory analyses of patients under age 50 years with 1-3 positive nodes and RS ≤25 showed improved overall survival in IDC patients who received chemotherapy, but not among those with ILC. CONCLUSION: Our findings highlight the importance of lobular-specific tools for stratifying clinical and genomic risk, as well as the need for histologic subtype-specific analyses in randomized trials.

Sarcopenic visceral obesity is associated with increased post-liver transplant mortality in acutely ill patients with cirrhosis.

"Sarcopenic obesity" refers to a condition of low muscle mass in the context of obesity, though may be difficult to assess in patients with cirrhosis who are acutely ill. We aimed to define sarcopenic visceral obesity (SVO) using CT-based skeletal muscle index (SMI) and visceral-to-subcutaneous adipose tissue ratio (VSR) to examine its association with post-transplant mortality. We analyzed 116 adult inpatients with cirrhosis who were urgently listed and transplanted between 1/2005 and 12/2017 at 4 North American transplant centers. SVO was defined as patients with sarcopenia (SMI <50 cm2 /m2 in men and <39 cm2 /m2 in women) and visceral obesity (VSR ≥ 1.54 in men and ≥1.37 in women). The percentage who met criteria for sarcopenia, visceral obesity, and SVO were 45%, 42%, and 20%, respectively. Cumulative rates of post-transplant mortality were higher in patients with SVO compared to patients with sarcopenia or visceral obesity alone at 36 months (39% vs. 14% vs. 8%) [logrank p = .01]. In univariable regression, SVO was associated with post-transplant mortality (HR 2.92, 95%CI 1.04-8.23) and remained significant after adjusting for age, sex, diabetes, encephalopathy, hepatocellular carcinoma, and MELD-Na (HR 3.50, 95%CI 1.10-11.15). In conclusion, SVO is associated with increased post-transplant mortality in acutely ill patients with cirrhosis.