Vascular stenting of a malignant arterial blowout as a bridge to effective systemic and regional therapy.

Locally advanced cutaneous squamous cell carcinoma can erode into blood vessels, leading to vascular blowout, requiring emergent surgical intervention. We describe a first case of this disease complication which was effectively managed with endovascular stenting as a bridge to effective systemic and regional therapy. We discuss the efficacy of this staged approach which is novel and timely in a clinical environment of increasingly effective systemic therapies.

Quality of Surgical Care Within the Criminal Justice Health Care System.

Importance: Individuals who are incarcerated represent a vulnerable group due to concerns about their ability to provide voluntary and informed consent, and there are considerable legal protections regarding their participation in medical research. Little is known about the quality of surgical care received by this population. Objective: To evaluate perioperative surgical care provided to patients who are incarcerated within the Texas Department of Criminal Justice (TDCJ) and compare their outcomes with that of the general nonincarcerated population. Design, Setting, and Participants: This cohort study analyzed data from patients who were incarcerated within the TDCJ and underwent general or vascular surgery at the University of Texas Medical Branch (UTMB) from 2012 to 2021. Case-specific outcomes for a subset of these patients and for patients in the general academic medical center population were obtained from the American College of Surgeons National Quality Improvement Program (ACS-NSQIP) and compared. Additional quality metrics (mortality index, length of stay index, and excess hospital days) from the Vizient Clinical Data Base were analyzed for patients in the incarcerated and nonincarcerated groups who underwent surgery at UTMB in 2020 and 2021 to provide additional recent data. Patient-specific demographics, including age, sex, and comorbidities were not available for analysis within this data set. Main Outcome and Measures: Perioperative outcomes (30-day morbidity, mortality, and readmission rates) were compared between the incarcerated and nonincarcerated groups using the Fisher exact test. Results: The sample included data from 6675 patients who were incarcerated and underwent general or vascular surgery at UTMB from 2012 to 2021. The ACS-NSQIP included data (2012-2021) for 2304 patients who were incarcerated and 602 patients who were not and showed that outcomes were comparable between the TDCJ population and that of the general population treated at the academic medical center with regard to 30-day readmission (6.60% vs 5.65%) and mortality (0.91% vs 1.16%). However, 30-day morbidity was significantly higher in the TDCJ population (8.25% vs 5.48%, P = .01). The 2020 and 2021 data from the Vizient Clinical Data Base included 629 patients who were incarcerated and 2614 who were not and showed that the incarcerated and nonincarcerated populations did not differ with regard to 30-day readmission (12.52% vs 11.30%) or morbidity (1.91% vs 2.60%). Although the unadjusted mortality rate was significantly lower in the TDCJ population (1.27% vs 2.68%, P = .04), mortality indexes, which account for case mix index, were similar between the 2 populations (1.17 vs 1.12). Conclusions and Relevance: Findings of this cohort study suggest that patients who are incarcerated have equivalent rates of mortality and readmission compared with a general academic medical center population. Future studies that focus on elucidating the potential factors associated with perioperative morbidity and exploring long-term surgical outcomes in the incarcerated population are warranted.

Timing of Adjuvant Immunotherapy in Stage III Melanoma, Does it Matter?

BACKGROUND: The optimal time to initiate adjuvant immune checkpoint inhibitors (ICI) following resection remains undefined. Herein, we investigated the impact of time to adjuvant ICI on survival in patients with stage III melanoma. METHODS: Patients with resected stage III melanoma receiving adjuvant immune therapy were identified within a multi-institutional retrospective cohort. Patients were stratified by time to adjuvant ICI: within 6 weeks, 6-12 weeks, and greater than 12 weeks from surgery. Recurrence-free survival (RFS) was compared among time strata with Kaplan-Meier and Cox proportional hazards methods in the multi-institutional cohort. RESULTS: Altogether, 626 patients were identified within the multi-institutional cohort: 39% of patients initiated adjuvant ICI within 6 weeks, 42.2% within 6-12 weeks, and 18.8% greater than 12 weeks from surgery. In a multivariate Cox model, adjusting for histology, nodal tumor burden, and pathologic stage, we found that increased time to adjuvant ICI was associated with improved RFS. Patients who initiated adjuvant ICI within 6 weeks of surgery had worse RFS. These findings were preserved in a conditional landmark analysis and separate subgroups of patients with (1) new melanoma diagnoses, (2) occult stage III disease, and (3) those receiving anti-PD-1 monotherapy. CONCLUSIONS: Outcomes for patients with stage III melanoma are not compromised when adjuvant ICI is initiated beyond 6 weeks from resection. Additional work is needed to better understand the underlying mechanisms and implications of timing of adjuvant ICI on long-term outcomes.

Exposure to Agent Orange and Risk of Bladder Cancer Among US Veterans.

Importance: To date, limited data exist regarding the association between Agent Orange and bladder cancer, and the Institute of Medicine concluded that the association between exposure to Agent Orange and bladder cancer outcomes is an area of needed research. Objective: To examine the association between bladder cancer risk and exposure to Agent Orange among male Vietnam veterans. Design, Setting, and Participants: This nationwide Veterans Affairs (VA) retrospective cohort study assesses the association between exposure to Agent Orange and bladder cancer risk among 2 517 926 male Vietnam veterans treated in the VA Health System nationwide from January 1, 2001, to December 31, 2019. Statistical analysis was performed from December 14, 2021, to May 3, 2023. Exposure: Agent Orange. Main Outcomes and Measures: Veterans exposed to Agent Orange were matched in a 1:3 ratio to unexposed veterans on age, race and ethnicity, military branch, and year of service entry. Risk of bladder cancer was measured by incidence. Aggressiveness of bladder cancer was measured by muscle-invasion status using natural language processing. Results: Among the 2 517 926 male veterans (median age at VA entry, 60.0 years [IQR, 56.0-64.0 years]) who met inclusion criteria, there were 629 907 veterans (25.0%) with Agent Orange exposure and 1 888 019 matched veterans (75.0%) without Agent Orange exposure. Agent Orange exposure was associated with a significantly increased risk of bladder cancer, although the association was very slight (hazard ratio [HR], 1.04; 95% CI, 1.02-1.06). When stratified by median age at VA entry, Agent Orange was not associated with bladder cancer risk among veterans older than the median age but was associated with increased bladder cancer risk among veterans younger than the median age (HR, 1.07; 95% CI, 1.04-1.10). Among veterans with a diagnosis of bladder cancer, Agent Orange was associated with lower odds of muscle-invasive bladder cancer (odds ratio [OR], 0.91; 95% CI, 0.85-0.98). Conclusions and Relevance: In this cohort study among male Vietnam veterans, there was a modestly increased risk of bladder cancer-but not aggressiveness of bladder cancer-among those exposed to Agent Orange. These findings suggest an association between Agent Orange exposure and bladder cancer, although the clinical relevance of this was unclear.

Multicenter Experience with Neoadjuvant Therapy in Melanoma Highlights Heterogeneity in Contemporary Practice.

OBJECTIVE: To determine the feasibility and impact of neoadjuvant therapy (NT) in patients who present with advanced melanoma amenable to surgical resection. SUMMARY BACKGROUND DATA: Given current effective systemic therapy for melanoma, the use of NT is being explored in patients with advanced melanoma with disease amenable to surgical resection. METHODS: Prospective data from 3 institutions was obtained in patients with clinically evident Stage III/IV melanoma who underwent NT. The primary objective was to compare recurrence-free survival between patients who had pathologic complete response (pCR) to those with persistent disease. RESULTS: NT was offered to 45 patients, with 43 patients initiating various NT regimens including PD-1 antagonist (PD-1) therapy (N = 16), PD-1 plus ipilimumab (N = 10), BRAF/MEK inhibitor therapy (N = 14), a combination of those three (N = 1), and talimogene laherparepvec (TVEC) (N = 2). Thirty-two (74.1%) patients underwent surgery whereas 11 patients did not undergo surgery for these reasons: clinical CR (N = 7), progressive disease not amenable to resection (N = 3), and ongoing therapy (N = 1). 12 of 32 patients (37.5%) had pCR with these therapies: PD-1 (N = 4), PD-1 plus ipilimumab (N = 2), BRAF/MEK (N = 4), combination (N = 1), and TVEC (N = 1). At median follow-up of 16.4 months there was only 1 recurrence in the pCR group and patients with a pCR had significantly improved recurrence-free survival compared to patients without pCR (p = 0.004). CONCLUSIONS: Despite variability in NT regimens across institutions, NT for melanoma is feasible and associated with improved prognosis in patients who achieve a pCR. Maximizing rates of pCR could improve prognosis for patients with advanced melanoma.

Extracorporeal Membrane Oxygenation for Adult Patients With Neoplasms: Outcomes and Trend Over the Last 2 Decades.

Extracorporeal membrane oxygenation (ECMO) is utilized in the management of severe respiratory and circulatory failure. Advanced malignancy is a relative contraindication, but the indication for ECMO in the oncologic population has not been clearly established because of the wide spectrum of malignant disease and prognoses. The Extracorporeal Life Support Organization database was queried for patients older than 18 years with an International Classification of Diseases code of neoplasm over the past 2 decades (2000-2019). The data were divided into 2 decades to analyze and compare the trends with background and outcomes. One thousand six-hundred ninety-seven patients met inclusion criteria from the latest decade which is over 15 times the previous decade (n = 110). Compared with the previous decade, ECMO was used more in patients with older age (56 vs . 50.5 years old; p < 0.001), cardiac and extracorporeal cardiopulmonary resuscitation (ECPR) support type ( p = 0.011), and lower oxygenation index (23.0 vs . 35.6; p < 0.001) in the latest decade. Although overall survival did not show significant improvement overall (38.9% vs . 33.6%; p = 0.312), survival in pulmonary ECMO has significantly improved in the latest decade (41.6% vs . 29.1%; p = 0.032). Compared with the previously reported data for all adult ECMO, our patients had a significantly lower survival with pulmonary (41.6% vs . 61.1%; p < 0.001) and cardiac (38.4% vs . 44.3%; p = 0.008) support while not with ECPR.

Spatial biology analysis reveals B cell follicles in secondary lymphoid structures may regulate anti-tumor responses at initial melanoma diagnosis.

Introduction: B cells are key regulators of immune responses in melanoma. We aimed to explore differences in the histologic location and activation status of B cell follicles in sentinel lymph nodes (SLN) of melanoma patients. Methods: Flow cytometry was performed on fresh tumor draining lymph nodes (LN). Paraffin slides from a separate cohort underwent NanoString Digital Spatial Profiling (DSP)®. After staining with fluorescent markers for CD20 (B cells), CD3 (T cells), CD11c (antigen presenting cells) and a nuclear marker (tumor) was performed, regions of interest (ROI) were selected based on the location of B cell regions (B cell follicles). A panel of 68 proteins was then analyzed from the ROIs. Results: B cell percentage trended higher in patients with tumor in LN (n=3) compared to patients with nSLN (n=10) by flow cytometry. B cell regions from a separate cohort of patients with tumor in the (pSLN) (n=8) vs. no tumor (nSLN) (n=16) were examined with DSP. Within B cell regions of the SLN, patients with pSLN had significantly higher expression of multiple activation markers including Ki-67 compared to nSLN patients. Among 4 patients with pSLN, we noted variability in arrangement of B cell follicles which were either surrounding the tumor deposit or appeared to be infiltrating the tumor. The B cell follicle infiltrative pattern was associated with prolonged recurrence free survival. Conclusion: These data suggest a role for B cell follicles in coordinating effective adaptive immune responses in melanoma when low volume metastatic disease is present in tumor draining LN.

Characterizing molecular subtypes of high-risk non-muscle-invasive bladder cancer in African American patients.

BACKGROUND: We sought to determine whether differences in subtype distribution and differentially expressed genes exist between African Americans (AAs) and European Americans (EAs) in patients with high-risk nonmuscle-invasive bladder cancer (NMIBC). METHODS: We performed a retrospective cohort study including 26 patients (14 AAs and 12 EAs) from the University of Texas Medical Branch and the Durham Veterans Affair Health Care System from 2010 to 2020 among treatment naïve, high-risk NMIBC. Profiled gene expressions were performed using the UROMOL classification system. RESULTS: UROMOL racial subtype distributions were similar with class 2a being most common with 10 genes commonly upregulated in AAs compared to EAs including EFEMP1, S100A16, and MCL1 which are associated with progression to muscle-invasive bladder cancer, mitomycin C resistance, and bacillus Calmette-Guérin durability, respectively. We used single nuclei analysis to map the malignant cell heterogeneity in urothelial cancer which 5 distinct malignant epithelial subtypes whose presence has been associated with different therapeutic response prediction abilities. We mapped the expression of the 10 genes commonly upregulated by race as a function of the 5 malignant subtypes. This showed borderline (P = 0.056) difference among the subtypes suggesting AAs and EAs may be expected to have different therapeutic responses to treatments for bladder cancer. AAs were enriched with immune-related, inflammatory, and cellular regulation pathways compared to EAs, yet appeared to have reduced levels of the aggressive C3/CDH12 bladder tumor cell population. CONCLUSIONS: While premature, gene expression differed between AAs and EAs, supporting potential race-based etiologies for muscle-invasion, response to treatments, and transcriptome pathway regulations.

Comparing costs of renal preservation versus radical nephroureterectomy management among patients with non-metastatic upper tract urothelial carcinoma.

BACKGROUND: To describe overall and categorical cost components in the management of patients with non-metastatic upper tract urothelial carcinoma (UTUC) according to treatment. METHODS: We identified 4,114 patients diagnosed with non-metastatic UTUC from 2004 to 2013 in the Survival Epidemiology and End Results-Medicare linked database. Patients were stratified into renal preservation (RP) vs. radical nephroureterectomy (NU) groups. Total Medicare costs within 1 year of diagnosis were compared for patients managed with RP vs. NU using inverse probability of treatment-weighted propensity score models. RESULTS: A total of 1,085 (26%) and 3,029 (74%) patients underwent RP and NU, respectively. Median costs were significantly lower for RP vs. NU at 90 days (median difference -$4,428, Hodges-Lehmann [H-L] 95% confidence interval [CI], -$7,236 to -$1,619) and 365 days (median difference -$7,430, H-L 95% CI, -$13,166 to -$1,695), respectively. Median costs according to categories of services were significantly less for RP vs. NU patients by hospitalization, office visits, emergency room/critical care, consultations, and anesthesia. The only category which was significantly higher for RP vs. NU was inpatient visits ($1,699 vs. $1,532; median difference $152; HL 95% CI, $19-$286). CONCLUSIONS: Median costs were significantly lower for RP vs. NU up to 1-year and by hospitalization, office visits, emergency room/critical care, consultations, and anesthesia costs. In appropriately selected patients, such as patients with low-risk disease, these findings suggest the utility of RP as a suitable high-value management option in UTUC.

Management, Surveillance Patterns, and Costs Associated With Low-Grade Papillary Stage Ta Non-Muscle-Invasive Bladder Cancer Among Older Adults, 2004-2013.

Importance: Low-risk non-muscle-invasive bladder cancer (NMIBC) is associated with extremely low rates of progression and cancer-specific mortality; however, patients with low-risk NMIBC may often receive non-guideline-recommended and potentially costly surveillance testing and treatment. Objective: To describe current surveillance and treatment practices, cancer outcomes, and costs of care for low-grade papillary stage Ta (low-grade Ta) NMIBC and identify factors associated with increased cost of care. Design, Setting, and Participants: This population-based cohort study identified 13 054 older adults (aged 66-90 years) diagnosed with low-grade Ta tumors in the Surveillance, Epidemiology and End Results-linked Medicare database from January 1, 2004, through December 31, 2013. Medicare claims data through December 31, 2014, were also reviewed. Data were analyzed from April 1 to October 6, 2021. Exposures: Surveillance testing and treatment among patients with low-grade Ta NMIBC. Main Outcomes and Measures: The primary outcome was patterns in population-level surveillance and treatment practice over time among patients with low-grade Ta NMIBC. Secondary outcomes were recurrence (defined as receipt of subsequent transurethral resection of bladder tumor >3 months after index diagnosis of NMIBC and initial transurethral resection of bladder tumor), progression (defined as receipt of definitive treatment for bladder cancer), and costs of care. Results: Among 13 054 patients who met inclusion criteria, 9596 (73.5%) were male and 3458 (26.5%) were female, with a median age of 76 years (IQR, 71-81 years). A total of 403 patients (3.1%) were Black, 120 (0.9%) were Hispanic, 12 123 (92.9%) were White, and 408 (3.1%) were of other races and/or ethnicities. Rates of surveillance cystoscopy increased over the study period (from 79.3% in 2004 to 81.5% in 2013; P = .007), with patients receiving a median of 3.0 cystoscopies per year (IQR, 2.0-4.0 per year). Rates of upper tract imaging (particularly computed tomography or magnetic resonance imaging) also increased over the study period (from 30.4% in 2004 to 47.0% in 2013; P < .001), with most patients receiving a median of 2.0 imaging tests per year (IQR, 1.0-2.0 per year). The use of urine cytologic testing or other urine biomarker assessment also increased (from 44.8% in 2004 to 54.9% in 2013; P < .001). Rates of adherence to current guidelines were similar over time (eg, a median of 4398 patients [55.2%] received ≤2 cystoscopies per year in 2004-2008 vs a median of 2736 patients [53.8%] in 2009-2013; P = .11), suggesting overuse of all surveillance testing modalities. With regard to treatment, 2250 patients (17.2%) received intravesical bacillus Calmette-Guérin, and 792 patients (6.1%) received intravesical chemotherapy (excluding receipt of a single perioperative dose). Among all patients with low-grade Ta NMIBC, 217 (1.7%) experienced disease recurrence and 52 (0.4%) experienced disease progression. The total annual median costs of low-grade Ta surveillance testing and treatment increased by 60% (from $34 792 in 2004 to $53 986 in 2013), with higher 1-year median expenditures noted among those with disease recurrence ($76 669) vs no disease recurrence ($53 909) at the end of the study period. Conclusions and Relevance: In this cohort study, despite low rates of disease recurrence and progression, rates of surveillance testing increased during the study period. The annual cost of care also increased over time, particularly among patients with recurrent disease. Efforts to improve adherence to current practice guidelines, with the focus on limiting overuse of surveillance testing and treatment, may mitigate associated increasing costs of care.

Long term cost comparisons of radical cystectomy versus trimodal therapy for muscle-invasive bladder cancer.

BACKGROUND: Earlier studies on the cost of muscle-invasive bladder cancer treatments are limited to short-term costs of care. We determined the 2- and 5-year costs associated with trimodal therapy (TMT) vs. radical cystectomy (RC). METHODS: We performed a retrospective cohort study using the Surveillance, Epidemiology, and End Results (SEER)-Medicare database. Total Medicare costs at 2 and 5 years following RC vs. TMT were compared using inverse probability of treatment-weighted propensity score models. RESULTS: A total of 2,537 patients aged 66 to 85 years were diagnosed with clinical stage T2-4a muscle-invasive bladder cancer. Total median costs for patients that received no definitive treatment(s) were $73,780 and $88,275 at 2-and 5-years. Costs were significantly higher for TMT than RC at 2-years ($372,839 vs. $191,363, Median Difference $127,815, Hodges-Lehmann Estimate (H-L) 95% Confidence Interval (CI), $112,663-$142,966) and 5-years ($424,570 vs. $253,651, Median Difference $124,466, H-L 95% CI, $105,711-$143,221). TMT had higher outpatient costs than RC (2-years: $318,221 vs. $100,900; 5-years: $367,092 vs. $146,561) with significantly higher costs with radiology, medications, pathology/laboratory, and other professional services. RC had higher inpatient costs than TMT (2-years: $62,240 vs. $33,631, Median Difference $-29,174, H-L 95% CI, $-32,364-$-25,984; 5-years: $75,499 vs. $45,223, Median Difference $-29,843, H-L 95% CI, $-33,905-$-25,781). CONCLUSIONS AND RELEVANCE: The excess spending associated with trimodal therapy vs. radical cystectomy was largely driven by outpatient expenditures. The relatively high long-term trimodal therapy costs are prime targets for cost containment strategies to optimize future value-based care.

Quality Improvement Intervention Bundle Using the PUPPIES Acronym Reduces Pressure Injury Incidence in Critically Ill Patients.

OBJECTIVE: To assess whether a quality improvement bundle focusing on prevention is effective in reducing pressure injury (PI) incidence or costs or delaying PI onset. METHODS: A combined retrospective/prospective cohort study was performed at an academic tertiary care ICU on all patients admitted with a length of stay longer than 48 hours and Braden scale score of 18 or less. Following retrospective data collection (preintervention), a multimodal quality improvement bundle focusing on PI prevention through leadership initiatives, visual tools, and staff/patient education was developed, and data were prospectively collected (postintervention). RESULTS: Statistical and cost analyses were performed comparing both cohorts. A total of 930 patients met the study inclusion criteria (preintervention, n = 599; postintervention, n = 331). A significant decrease in PI incidence was observed from preintervention (n = 37 [6%]) to postintervention (n = 7 [2%], P = .005). This led to a predicted yearly cost savings of $826,810. Further, a significant increase in time to PI occurrence was observed from preintervention (mean, 5 days) to postintervention (mean, 9 days; P = .04). Staff were compliant with the bundle implementation 80% of the time. CONCLUSIONS: Implementation of the quality improvement bundle focused on multimodal PI prevention in critically ill patients led to a significant reduction in PI incidence, increased time to PI occurrence, and was cost-effective.

How much time is enough? Sentinel lymph node mapping time depends on the radiotracer agent.

BACKGROUND: In 2014, technetium-99m tilmanocept (TcTM) replaced technetium-99m sulfur colloid (TcSC) as the standard lymphoscintigraphy (LS) mapping agent in melanoma patients undergoing sentinel lymph node biopsy (SLNB). The aim of this study was to examine differences in mapping time, intra-operative identification of sentinel lymph node (SLN), and false negative rate (FNR) between patients who underwent SLNB with TcTM compared to TcSC. METHODS: Patients who underwent SLNB between 2010 and 2018 were retrospectively identified. Patient demographic, tumor, and imaging data was stratified by receipt of TcSC (n = 258) or TcTM (n = 133). Student's t test and χ2 test were used to compare characteristics and outcomes. RESULTS: Both cohorts were similar in demographic, primary tumor characteristics, and total number of SLN identified (TcTM 3.56 vs. TcSC 3.28, p = 0.244). TcTM was associated with significantly shorter LS mapping times (51.8 vs. 195.1 min, p < 0.01). There was no significant difference in the number of patients with positive SLN (TcTM 11.3 vs. TcSC 17.4%, p = 0.109) and the FNR was similar between both groups (TcTM 25% vs. TcSC 22%). CONCLUSION: TcTM was associated with significantly shorter LS mapping time while identifying similar numbers of SLN. Our results support further study to ensure similar FNR and oncologic outcomes between agents.

Optimizing outcomes in colorectal surgery: cost and clinical analysis of robotic versus laparoscopic approaches to colon resection.

The use of robotics in colorectal surgery has been steadily increasing, however, reported longer operative times and increased cost has limited its widespread adoption. We investigated the cost of elective colorectal surgery based on type of anatomic resection and the impact of a standardized protocol for robotic colectomies. A retrospective review was conducted of 279 elective colectomies at a single institution between 2013 and 2017. Clinical outcomes and detailed cost data were compared based on open, laparoscopic, or robotic surgical approach and stratified by anatomic resection. Robotic, laparoscopic and open colectomy rates were 35, 34 and 31%, respectively. While total costs were similar in robotic and laparoscopic surgery, anatomic resection stratification showed that low anterior resection (LAR) was significantly cheaper ($14,093 vs $17,314). When a standardized surgical protocol was implemented for robotic colectomies, significant reductions in operative times, length of stay, total cost, and operative cost were observed. Robotic surgery may be most cost effective for elective LAR compared to laparoscopic or open approaches. A standardized surgical protocol for robotic surgery may help reduce costs by reducing operative times, operating rooms expenditure, and lengths of stay.