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Objective: Melanoma survival has greatly improved with the advent of immunotherapy, but unequal access to these medications may exist due to nonmedical patient factors such as insurance status, educational background, and geographic proximity to treatment., Methods: We used the National Cancer Database to assess patients with nonmetastatic cutaneous melanoma who underwent surgical resection and sentinel lymph node biopsy (SLNB) with tumor involvement from 2015 to 2020. We evaluated rates of adjuvant immunotherapy among this patient population based on patient, tumor, and facility variables, including insurance status, socioeconomic status, pathologic stage (IIIA-IIID), and treatment facility type and volume., Results: Adjuvant immunotherapy was associated with improved survival for stage III melanoma, with a slight increase in 5-year OS for stage IIIA (87.9% vs. 85.9%, P=0.044) and a higher increase in stages IIIB-D disease (70.3% vs. 59.6%, P<0.001). Receipt of adjuvant immunotherapy was less likely for patients who were older, low socioeconomic status, or uninsured. Low-volume and community cancer centers had higher rates of adjuvant immunotherapy overall for all stage III patients, whereas high-volume and academic centers used adjuvant immunotherapy much less often for stage IIIA patients compared with those in stages IIIB-D., Conclusions: Our results demonstrate inconsistent use of adjuvant immunotherapy among patients with stage III melanoma despite a significant association with improved survival. Notably, there was a lower use of adjuvant immunotherapy in patients of lower SES and those treated at high-volume centers. Equity in access to novel standards of care represents an opportunity to improve outcomes for patients with melanoma., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Sentinel lymph node biopsy (SLNB) is performed less often for older patients with melanoma. We investigated the association of SLNB and melanoma-specific survival (MSS) in the elderly., Methods: We retrospectively reviewed the Surveillance, Epidemiology, and End Results (SEER: 2010-2019) for patients ≥ 70 years with cT2-4N0M0 melanoma. We used multivariable Cox proportional hazard models to evaluate the impact of SLNB performance and SLN status on MSS at increasing age cutoffs. In addition, we evaluated the association of different factors with SLNB performance using multivariable logistic regression., Results: We identified 11,548 patients. Sentinel lymph node biopsy occurred in 6754 (58.5%) patients, 1050 (15.5%) of whom had a positive SLN. On adjusted SEER analysis, a negative SLN was independently associated with improved MSS (overall hazard ratio [HR] 0.59, 95% confidence interval [CI] 0.63-0.67) for patients up to 87 years old. Positive SLNB was independently associated with inferior MSS (HR 1.71, 95% CI 1.93-1.98). Increasing age groups were significantly associated with decreased SLNB performance., Conclusions: Sentinel lymph node biopsy is associated with cancer-specific survival and adds prognostic information for elderly patients with melanoma. Sentinel lymph node biopsy performance should not be eliminated in elderly patients based on age alone, unless justified by poor performance status, patient preference, or other surgical contraindications. Decreased SLNB performance with increasing age in our cohort may indicate a missed therapeutic opportunity in the care of elderly patients with melanoma., (© 2024. The Author(s).)

Introduction: Upper gastrointestinal (UGI) cancers require multidisciplinary treatment, but surgery provides the only potentially curative option. We sought to understand reasons for attrition before surgery within our regional hospital network., Methods: We performed chart reviews of patients (age 18-80) with stage I-III UGI cancers (gastroesophageal junction, gastric, and hepatopancreatobiliary adenocarcinomas) in our multihospital cancer registry from 2015 to 2021. Our primary outcome was reasons for surgical attrition. Univariable analysis identified factors related to surgical attrition and the Kaplan-Meier method estimated overall survival based on surgery receipt., Results: Seven hundred and ninety-two patients were included in our analysis, of whom 107 (13.5%) did not undergo curative surgery. Reasons for not undergoing surgery included medical comorbidities (30.8%), patient preference/nonmedical barriers (24.3%, which included: not interested without further explanation, worried about complications, nonadherence to appointments, insurance issues, did not wish for blood transfusion, lack of social support, preferring home care, and worried about recurrence), psychosocial (5.6%), progression while on neoadjuvant therapy or waiting for transplant (15.0% and 7.5%), poor performance status (3.7%), side effects of neoadjuvant therapy (3.7%), and death unrelated to treatment or unknown cause (9.4%). Nonsurgical management was not associated with race, socioeconomic status, or distance traveled for care. Survival was greatly improved for patients who underwent surgery (158 vs. 63 weeks, p < 0.05)., Conclusion: Nearly one in seven patients (18-80 years old) with UGI cancers evaluated at our academic cancer center did not undergo surgical resection. Reasons for surgical attrition included potentially modifiable issues, and addressing these barriers could help overcome inequities in cancer treatment and survival., (© 2024 Wiley Periodicals LLC.)

Introduction: The NCCN considers "baseline staging" (whole body CT or PET scan +/- brain MRI) for all asymptomatic melanoma patients with a positive sentinel lymph node biopsy. The true yield of these workups is unknown., Methods: We created cohorts of adult malignant melanoma patients, using the National Cancer Database (2012-2020) to mimic three common scenarios: (1) clinically node negative, with positive sentinel lymph node(s) (SLNB[+]); (2) clinically node negative, with negative sentinel lymph node(s) (SLNB[-]); (3) clinically node positive with confirmed lymph node metastases (cN[+] and pN[+]). Multivariable regression, supervised decision trees, and nomograms were constructed to assess the risk of metastases based on key features., Results: 10,371 patients were SLNB[+], 55,172 were SLNB[-], and 4,012 were cN[+] and pN[+]. The proportion of patients with any metastatic disease (brain metastases) were as follows: SLNB[+]: 1.4% (0.3%); SLNB[-] 0.3% (<0.1%); cN[+] and pN[+] 11.6% (1.6%). On multivariable regression, Breslow depth > 4, ulceration, and lymphovascular invasion were associated with greater risk of metastatic disease. A supervised decision tree for SLNB[+] and SLNB[-] patients found the only groups with >2% risk of metastases were T4 tumors or T2/T3 tumors with ulceration and LVI. Most groups had a negligible risk (<0.1%) of brain metastases., Conclusion: This is the first large analysis to guide the use of imaging for cutaneous melanoma. Among clinically node negative patients, metastatic disease is uncommon and brain metastases are exceedingly rare. Further investigation could promote a tailored approach to metastatic workups guided by individual risk factors., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Socioeconomic factors influence the survival of patients with early stage melanoma and thus should be accounted for in prognostication tools.

Melanoma metabolism can be reprogrammed by activating BRAF mutations. These mutations are present in up to 50% of cutaneous melanomas, with the most common being V600E. BRAF mutations augment glycolysis to promote macromolecular synthesis and proliferation. Prior to the development of targeted anti-BRAF therapies, these mutations were associated with accelerated clinical disease in the metastatic setting. Combination BRAF and MEK inhibition is a first line treatment option for locally advanced or metastatic melanoma harboring targetable BRAF mutations. This therapy shows excellent response rates but these responses are not durable, with almost all patients developing resistance. When BRAF mutated melanoma cells are inhibited with targeted therapies the metabolism of those cells also changes. These cells rely less on glycolysis for energy production, and instead shift to a mitochondrial phenotype with upregulated TCA cycle activity and oxidative phosphorylation. An increased dependence on glutamine utilization is exhibited to support TCA cycle substrates in this metabolic rewiring of BRAF mutated melanoma. Herein we describe the relevant core metabolic pathways modulated by BRAF inhibition. These adaptive pathways represent vulnerabilities that could be targeted to overcome resistance to BRAF inhibitors. This review evaluates current and future therapeutic strategies that target metabolic reprogramming in melanoma cells, particularly in response to BRAF inhibition., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Characteristics of children with impaired development who have acute appendicitis are not well described in the literature., Methods: We reviewed the National Surgical Quality Improvement Program-Pediatric and the multicenter Pediatric Health Information System for patients with acute appendicitis. Comparisons for demographics, clinical outcomes, and hospital charges between children with impaired development versus neurotypical children were made using independent t test or Wilcoxon rank sum tests. The multivariable logistic regression model estimated the odds of complicated acute appendicitis in impaired development patients. Based on correlation analyses, hierarchical linear modeling was used to examine the extent to which impaired development influenced resource use., Results: Patients with impaired development were younger, had higher comorbidities, and were more commonly male sex. In the National Surgical Quality Improvement Program-Pediatric database, impaired development was associated with higher rates of complicated acute appendicitis (33.6% vs 27.5, P < .001), particularly in older children, and higher usage of computed tomography at National Surgical Quality Improvement Program-Pediatric hospitals (23.1% vs 15.1%, P < .001). In the Pediatric Health Information System database, the adjusted odds of complicated acute appendicitis were significantly higher in patients with impaired development (1.20 [1.09-1.31]), low childhood opportunity level (1.39 [95% confidence interval: 1.31-1.47]), and Black race (1.25 [1.17-1.33]). Hierarchical adjusted linear modeling showed that impaired development was associated with significantly higher hospital charges (9% increase)., Conclusion: Management of acute appendicitis in children with impaired development remains a challenge to clinicians, as evidenced by the higher rate of perforated appendicitis in older children, diagnostic computed tomography use at National Surgical Quality Improvement Program-Pediatric hospitals, postoperative computed tomography use, and increased costs., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objectives: Immune checkpoint inhibitors are a promising new therapy for advanced Merkel Cell Carcinoma (MCC). We investigated real-world utilization and survival outcomes of first-line immunotherapies in a contemporary cohort., Methods: Using the National Cancer Database (NCDB), we identified 759 patients with MCC between 2015 and 2020 with stage IV disease and known status of first-line systemic therapy. Univariable and multivariable analyses were used to determine predictors of immunotherapy usage. Overall survival (OS) was compared for patients receiving immunotherapy, chemotherapy, or no systemic therapies., Results: We identified 759 patients meeting our inclusion criteria: 329 patients received immunotherapy, 161 received chemotherapy, and 269 received no systemic therapy. Adjusting for demographic, clinical, and facility factors, high facility volume significantly predicted first-line immunotherapy use (OR 1.99; P =0.017). Median OS was 16.2, 12.3, and 8.7 months, among patients who received immunotherapy, chemotherapy, or no systemic therapy, respectively ( P <0.001). On Cox multivariable survival analysis, first-line immunotherapy treatment (HR=0.79, P =0.041) and treatment at high-volume centers (HR=0.58, P =0.004) were associated with improved OS., Conclusions: Consistent with clinical trial results, first-line immunotherapy associated with improvement in median overall survival for patients with stage IV MCC, significantly outperforming chemotherapy in this real-world cohort. Treatment at high-volume centers associated with first-line immunotherapy utilization suggesting that familiarity with this rare disease is important to achieving optimal outcomes for metastatic MCC., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: The optimal surgical option in patients with multifocal hepatocellular carcinoma (MHCC) is an area of active research. The preference varies based on geographic variations and institutional policies. We sought to determine long-term outcomes in patients with MHCC based on surgical treatment-liver transplant (LT) vs resection (LR)., Methods: We performed a retrospective analysis of the National Cancer Database (2004-2015) and identified patients with MHCC within Milan criteria. Patients with α-fetoprotein ≥ 1000 ng/mL and those who underwent ablation were excluded. The primary outcome measure was long-term survival in patients undergoing LT vs LR. The secondary aim of our study was to determine clinicodemographic factors associated with the receipt of LT and LR., Results: A total of 1546 patients were included, of whom 1211 received LT and 335 underwent LR. Patients who were non-Hispanic White (70.8% vs 54.9%; P < .01), privately insured (53.7% vs 36.7%; P < .01), and treated at academic centers (85.4% vs 71.6%; P < .01) were more likely to receive an LT. Multivariable Cox analysis revealed LT was associated with improved survival compared with LR (hazard ratio, 0.34; 95% CI, 0.28-0.42)., Conclusion: We described clinical and sociodemographic differences in LT and LR patients and found LT to be associated with a decreased mortality risk compared with LR. The study's findings should be interpreted in the context of several limitations, including the selection of MHCC criteria within Milan criteria., (Copyright © 2024 Society for Surgery of the Alimentary Tract. Published by Elsevier Inc. All rights reserved.)

Background: Survival data on patients with locally advanced rectal cancer (LARC) undergoing non-operative management (NOM) in a real-world setting are lacking., Methods: We analyzed LARC patients from the National Cancer Database with the following features: treated between 2010 and 2020, age 18-65 years, Charlson comorbidity index (CCI) ≤ 1, received neoadjuvant multiagent chemotherapy plus radiation ≥ 45 Gray, and underwent surgery or NOM. Patients were stratified into two groups: (A) clinical T1-3 tumors with positive nodes (cT1-3N+) and (B) clinical T4 tumors, N+/- (cT4N+/-). We performed a comparative analysis of overall survival (OS) with NOM versus surgery by the Kaplan-Meier method and propensity score matching. Additionally, a multivariable analysis explored the association between NOM and OS., Results: NOM exhibited significantly lower OS than surgery in both groups. In cT1-3N+ patients, NOM resulted in a 5-year OS of 73.9% (95% confidence interval [CI] = 69.7-77.6%) versus 84.5% (95% CI = 83.6-85.3%) with surgery ( p < 0.001). In the cT4N+/- group, NOM yielded a 5-year OS of 44.5% (95% CI = 37.0-51.8%) versus 72.5% (95% CI = 69.9-74.8%) with surgery ( p < 0.001). Propensity score matching and multivariable analyses revealed similar conclusions., Conclusion: Patients with LARC undergoing NOM versus surgery in real-world settings appear to have inferior survival.

Background: In 2011, immunotherapy and targeted therapy revolutionized melanoma treatment. However, inequities in their use may limit the benefits seen by certain patients., Methods: We performed a retrospective review of patients in the National Cancer Database for patients with stage IV melanoma from 2 time periods: 2004-2010 and 2016-2020, distinguishing between those who received systemic therapy and those who did not. We investigated the rates and factors associated with treatment omission. We employed Kaplan-Meier analysis to explore the impact of treatment on overall survival., Results: A total of 19,961 patients met the inclusion criteria: 7621 patients were diagnosed in 2004-2010 and 12,340 patients in 2016-2020, of whom 54.9% and 28.3% did not receive systemic treatment, respectively. The rate of "no treatment" has decreased to a plateau of ∼25% in 2020. Median overall survival was improved with treatment in both time periods (2004-2010: 8.8 vs. 5.6 mo [ P <0.05]; and 2016-2020: 25.9 vs. 4.3 mo [ P <0.05]). Nonmedical factors associated with the omission of treatment in both periods included low socioeconomic status, Medicaid or no health insurance, and treatment at low-volume centers. In the period from 2016 to 2020, patients treated at nonacademic programs were also less likely to receive treatment., Conclusions: Systemic therapies significantly improve survival for patients with metastatic melanoma, but significant disparities exist with their receipt. Local efforts are needed to ensure all patients benefit from these revolutionary treatments., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: The management of T2 multifocal hepatocellular carcinoma (MHCC) is controversial, and the comparative impact of liver resection (LR) versus tumor ablation (TA) on survival continues to be debated. The aim of our study was to examine short- and long-term survival for LR and TA in a nationally representative cohort. We hypothesized that patients who underwent LR would have improved survival., Methods: We utilized the National Cancer Database (2004-2015) to identify patients diagnosed with non-metastatic T2 MHCC. Kaplan-Meier survival curves were generated to compare 10-year overall survival (OS) between LR and TA patients. Kaplan-Meier analysis with stratification was also performed based on lymphovascular invasion, resection margin status, and Charlson-Deyo score. Cox proportional hazard models were used in multivariable analyses., Results: A total of 1225 patients met the inclusion criteria. 991 patients received LR, and 234 received TA. The majority of patients were male, White, and older than ≥60 years old. Clinicodemographic characteristics were generally similar between LR and TA patients. Among patients who underwent LR, 84% had negative margins, and 17% had lymphovascular invasion. Mortality at 30 days was significantly higher among LR patients compared to TA patients (5.4% vs 0.0%, p < 0.001), with those having a Charlson-Deyo score ≥2 facing the highest risk at 7.3%. Nevertheless, 10-year OS for the LR cohort was 27.5% (95% confidence interval [CI]: 24.4%-30.8%) versus 14.7% (95% CI: 9.8%-20.7%, p < 0.001) for TA patients. In stratified analysis, survival benefit was statistically significant only among those with negative resection margin, no lymphovascular invasion, and Charlson-Deyo score ≤1. In multivariable Cox analysis, LR was independently associated with improved survival compared to TA (hazard ratio: 0.80; 95% CI = 0.67-0.95)., Conclusion: LR poses a higher long-term survival benefit than TA. Prospective studies are warranted to confirm these findings. Although our study patients are a highly selected group of multifocal T2 patients, it gives us a good insight into the fact that LR provides better outcomes if a transplant option is unavailable., (© 2024 The Authors. Journal of Surgical Oncology published by Wiley Periodicals LLC.)

Background and Objectives: There is no consensus guidelines on the best timing to perform Sentinel lymph node biopsy (SLNB) in high-risk melanoma patients. We aimed to understand the impact of surgical timing on nodal upstaging in patients with cutaneous melanoma., Methods: We queried the National Cancer Database from 2004 to 2018 for patients with T2-T4, N0, M0 melanomas, who underwent melanoma excision and nodal surgery. We included patients who underwent surgery within 2-19 weeks postdiagnosis. We aimed to determine the association of surgical delay (weeks) with nodal positivity., Results: A total of 53 355 patients were included, of whom 20.9% had positive lymph nodes. Patients underwent surgery at a median of 5 (4-7) weeks after diagnosis. The rate of positive nodes increased with increased weeks to surgery (line of best-fit slope = 0.38). Multivariable regression analysis identified an association between time to surgery and nodal positivity (2.4% increased risk per week, p < 0.05). Our analysis showed significantly increased likelihood of nodal positivity beginning 9 weeks after diagnosis (odds ratio [OR] = 1.3, p < 0.05). Furthermore, patients with T2-3 tumors had a significant increase in nodal positivity with increased time to surgery (OR = 1.03 per week, p < 0.001). However, no significant trend in nodal positivity was identified for patients with T4 melanomas (OR = 1.01 per week, p = 0.596)., Conclusion: Surgery within 9 weeks of melanoma diagnosis was not associated with increased likelihood of nodal positivity. These data can guide clinical conversations regarding the importance of surgical timing for melanoma., (© 2023 Wiley Periodicals LLC.)

Objectives: We used a novel combined analysis to evaluate various factors associated with failure to undergo surgery in non-metastatic pancreatic cancer., Methods: We identified rates of surgery and reasons for surgical attrition from clinical trials, which studied neoadjuvant therapy in resectable pancreatic cancer. Next, we queried the National Cancer Database (NCDB) for Stage I-III, T1-3 pancreatic adenocarcinoma patients. We investigated the rates and factors associated with the receipt of surgery. Finally, we evaluated variable importance predicting the receipt of surgery., Results: In clinical trials, 25-30 % of patients did not undergo surgery, mostly due to disease progression. In the NCDB, the overall surgical rate was only 49 %, but increased to 67 % in a curated cohort meant to mirror clinical trial patients. Patients treated at low-volume institutions (OR = 0.64, 95 % CI: 0.61-0.67) and who were uninsured (OR = 0.56, 95 % CI: 0.52-0.62) and Medicaid-insured (OR = 0.67, 95 % CI: 0.64-0.71) were less likely to receive potentially curative surgery., Conclusion: We have identified a realistic target surgery rate of 70%-75 % in potentially-resectable pancreatic cancer. While attrition to pancreatic cancer surgery is mostly due to tumor biology, our study identified the most important non-medical barriers, such as facility volume and insurance, affecting pancreatic cancer surgery., (Copyright © 2023 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Background and Objectives: Sentinel lymph node biopsy (SLNB) is an area of debate in the management of lentigo maligna melanoma (LMM). The utility of SLNB and its prognostic value in LMM have not yet been studied with large databases., Methods: We performed a retrospective review of the National Cancer Database (2012-2020) and the Surveillance, Epidemiology, and End Results (2010-2019) database for patients with cutaneous nonmetastatic LMM with Breslow thickness >1.0 mm. Multivariable logistic regression identified factors associated with SLNB performance and sentinel lymph node (SLN) positivity. Univariable and multivariable analyses assessed overall survival (OS) and melanoma-specific survival (MSS) based on SLNB performance and SLN status., Results: Compared to other melanoma subtypes, LMM had lower rates of SLNB (66.6% vs. 80.0%-84.0%) and SLN positivity (11.3% vs. 18.6%-34.2%). Compared to patients who did not undergo SLNB, SLN status was significantly associated with improved OS in patients with SLN positive (HR = 0.64 [0.55-0.76]) and SLN negative (HR = 0.68 [0.49-0.94]), and worse MSS only in patients with positive SLN (HR = 3.93, p < 0.05)., Conclusion: The improved OS associated with SLNB likely implies surgical selection bias. Analysis of MSS confirms appropriate patient selection and suggests important prognostic value associated with SLN status. These results support continued SLNB for LMM patients according to standard guidelines., (© 2023 Wiley Periodicals LLC.)

Background: The surgical management of 1- to 2-cm neuroendocrine tumors of the appendix is an area of debate. We analyzed the clinical outcomes of appendectomy and compared them to right hemicolectomy., Methods: We queried the National Cancer Database to identify patients treated for 1- to 2-cm ANETs from 2004 to 2018. Patients were stratified by surgical approach (appendectomy vs. hemicolectomy). Multivariable models were used to identify factors associated with the choice of surgical approach and the association between surgical approach and overall survival., Results: Of the 3,189 patients we included, 1,573 (49.3%) underwent right hemicolectomy and 1,616 (50.7%) appendectomy. The appendectomy rate increased from 37.7% in 2004 to 58.9% in 2018. On multivariable analysis, patients with grade 2 and 3 tumors were less likely to undergo appendectomy alone (odds ratio = 0.41, 95% confidence interval = 0.26-0.66). Longer travel distance was associated with a higher likelihood of undergoing appendectomy (odds ratio = 2.52, 95% confidence interval = 1.15-5.51). After adjusting for tumor grade, appendectomy alone had similar survival to hemicolectomy (hazard ratio = 1.03, 95% confidence interval = 0.67-1.59)., Conclusion: In this updated analysis of the National Cancer Database, right hemicolectomy was not associated with improved overall survival compared to appendectomy alone for 1- to 2-cm neuroendocrine tumors of the appendix. Although patients with grade 2 or 3 tumors are more likely to undergo right hemicolectomy, this procedure may not improve their treatment or overall outcome., (Copyright © 2023 Elsevier Inc. All rights reserved.)

We reviewed phase II and III trials beginning after 2010 studying preoperative therapy in melanoma (61 trials). Compared to standard adjuvant treatment, neoadjuvant immune checkpoint inhibitors (ICIs) show improved outcomes with approximately 70-80% recurrence free survival at 2 years. Several biomarkers demonstrate predictive value for pathological response (higher PD-L1 expression) and survival (IFN-γ signatures, CD8 + cell density). A number of 'non-standard' treatment mechanisms are being studied in combination with ICI therapies such as TLR-9 agonists, and anti-LAG3 checkpoint inhibitors, which show promise for alternative therapy options in the neoadjuvant setting. Finally, trials for advanced unresectable melanomas show improved survival compared to definitive systemic treatment when upfront systemic therapies lead to resectability. To conclude, in the preoperative setting for melanoma, ICIs have potential to improve outcomes for patients, and will likely change the standard treatment approach for advanced resectable disease., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Published by Elsevier B.V.)

Background: Melanomas < 0.8 mm in Breslow depth have less than a 5% risk for nodal positivity. Nonetheless, nodal positivity is prognostic for this group. Early identification of nodal positivity may improve the outcomes for these patients., Objectives: To determine the degree to which ulceration and other high-risk features predict sentinel lymph node (SLN) positivity for very thin melanomas., Methods: The National Cancer Database was reviewed from 2012 to 2018 for patients with melanoma with Breslow thickness < 0.8 mm. Data were analysed from 7 July 2022 through to 25 February 2023. Patients were excluded if data regarding their ulceration status or SLN biopsy (SLNB) performance were unknown. We analysed patient, tumour and health system factors for their effect on SLN positivity. Data were analysed using χ2 tests and logistic regressions. Overall survival (OS) was compared by Kaplan-Meier analyses., Results: Positive nodal metastases were seen in 876 (5.0%) patients who underwent SLNB (17 692). Factors significantly associated with nodal positivity on multivariable analysis include lymphovascular invasion [odds ratio (OR) 4.5, P < 0.001], ulceration (OR 2.6, P < 0.001), mitoses (OR 2.1, P < 0.001) and nodular subtype (OR 2.1, P < 0.001). Five-year OS was 75% and 92% for patients with positive and negative SLN, respectively., Conclusions: Nodal positivity has prognostic significance for very thin melanomas. In our cohort, the rate of nodal positivity was 5% overall in these patients who underwent SLNB. Specific tumour factors (e.g. lymphovascular invasion, ulceration, mitoses, nodular subtype) were associated with higher rates of SLN metastases and should be used to guide clinicians in choosing which patients will benefit from SLNB., Competing Interests: Conflicts of interest: The authors declare no conflicts of interest., (© The Author(s) 2023. Published by Oxford University Press on behalf of British Association of Dermatologists. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: The National Comprehensive Cancer Network (NCCN) guidelines recommend adjuvant chemotherapy (AC) within 6-8 weeks of surgical resection for patients with stage III colon cancer. However, postoperative complications or prolonged surgical recovery may affect the receipt of AC. The aim of this study was to assess the utility of AC for patients with prolonged postoperative recovery., Methods: We queried the National Cancer Database (2010-2018) for patients with resected stage III colon cancer. Patients were categorized as having either normal or prolonged length of stay (PLOS: >7 days, 75th percentile). Multivariable Cox proportional hazard regression and logistic regressions were used to identify factors associated with overall survival and receipt of AC., Results: Of the 113,387 patients included, 30,196 (26.6%) experienced PLOS. Of the 88,115 (77.7%) patients who received AC, 22,707 (25.8%) initiated AC more than 8 weeks after surgery. Patients with PLOS were less likely to receive AC (71.5% vs. 80.0%, OR: 0.72, 95%CI=0.70-0.75) and displayed inferior survival (75 vs. 116 months, HR: 1.39, 95%CI=1.36-1.43). Receipt of AC was also associated with patient factors such as high socioeconomic status, private insurance, and White race (p<0.05 for all). AC within and after 8 weeks of surgery was associated with improved survival for patients with both normal LOS and PLOS (normal LOS: <8 weeks HR: 0.56, 95% CI: 0.54-0.59, >8 weeks HR: 0.68, 95% CI: 0.65-0.71; PLOS: <8 weeks HR: 0.51, 95% CI: 0.48-0.54, >8 weeks HR: 0.63, 95% CI 0.60-0.67). AC was associated with significantly improved survival if initiated up to 15 weeks postoperatively (normal LOS: HR: 0.72, 95%CI=0.61-0.85; PLOS: HR: 0.75, 95%CI=0.62-0.90), and very few patients (<3.0%) initiated AC beyond this time., Conclusion: Receipt of AC for stage III colon cancer may be affected by surgical complications or otherwise prolonged recovery. Timely and even delayed AC (>8 weeks) are both associated with improved overall survival. These findings highlight the importance of delivering guideline-based systemic therapies, even after complicated surgical recovery., (© 2023. The Society for Surgery of the Alimentary Tract.)

Background: Early in the coronavirus disease 2019 (COVID-19) pandemic, hydroxychloroquine (HCQ) drew substantial attention as a potential COVID-19 treatment based on its antiviral and immunomodulatory effects in vitro . However, HCQ showed a lack of efficacy in vivo , and different groups of researchers attributed this failure to the insufficient drug concentration in the lung following oral administration (HCQ is only available in the market in the tablet form). Delivering HCQ by inhalation represents a more efficient route of administration to increase HCQ exposure in the lungs while minimizing systemic toxicity. In this pilot study, the safety, tolerability, and pharmacokinetics of HCQ nebulizer solution were evaluated in healthy volunteers. Methods: Twelve healthy participants were included in this study and were administered 2 mL of HCQ01 solution (equivalent to 25 mg of HCQ sulfate) through Aerogen ® Solo, a vibrating mesh nebulizer. Local tolerability and systemic safety were assessed by forced expiratory volume in the first and second electrocardiograms, clinical laboratory results (e.g., hematology, biochemistry, and urinalysis), vital signs, and physical examinations. Thirteen blood samples were collected to determine HCQ01 systemic exposure before and until 6 hours after inhalation. Results: The inhalation of HCQ01 was well tolerated in all participants. The mean value of C max occurred at around 4.8 minutes after inhalation and rapidly decreased thereafter. The reported systemic exposure was very low with a mean value of 5.28 (0.6-15.6) ng·h/mL. T max occurred at around 4.8 minutes after inhalation and rapidly decreased thereafter. The reported systemic exposure was very low with a mean value of 5.28 (0.6-15.6) ng·h/mL. Conclusion: The low systemic concentrations of HCQ01 of 9.66 ng/mL reported by our study compared with 1 μg/mL previously predicted after 200 mg BID oral administration, and the safety and tolerability of HCQ01 administered as a single dose through nebulization, support the assessment of its efficacy, safety, and tolerability in further studies for the treatment of COVID-19.

Background: We determined the minimum threshold (Tmin) of annual facility case volume to optimize outcomes for patients with resected perihilar cholangiocarcinoma., Methods: We identified patients with localized perihilar cholangiocarcinoma who underwent resection within the National Cancer Database (2010-2017). We used marginal structural logistic regression models to estimate the average treatment effect of receiving care in facilities meeting/exceeding Tmin on 90-day mortality and other postoperative outcomes., Results: A total of 2471 patients underwent resection for perihilar cholangiocarcinoma at 471 facilities. There was no effect of total hepatopancreatobiliary, surgical hepatopancreatobiliary, total hepatobiliary, surgical hepatobiliary, or total perihilar cholangiocarcinoma case volume on 90-day mortality. A Tmin of seven perihilar cholangiocarcinoma resections/year resulted in lower odds of 90-day mortality (IP-weighted OR = 0.49, 95% CI: 0.66-0.87). A total of two facilities met the Tmin. Patients receiving treatment at Tmin facilities had lower odds of length of stay ≥ 7 days (IP-weighted OR = 0.85, 95% CI: 0.75-0.97) and positive surgical resection margins (IP-weighted OR = 0.40, 95% CI: 0.47-0.55). Additionally, undergoing surgery at Tmin facilities resulted in higher (≥ 4 nodes) lymph node yields (IP-weighted OR = 1.94, 95% CI: 1.21-3.11) but no change in the odds of nodal positivity. There was no effect of undergoing surgery at Tmin facilities on 30-day mortality or re-admission., Conclusions: Resection of perihilar cholangiocarcinoma is infrequently performed at a high number of facilities. A Tmin of ≥ 7 resections/year resulted in lower 90-day mortality and improved postoperative outcomes. Our data suggest that regionalization of care for patients with perihilar cholangiocarcinoma could potentially improve outcomes in the USA., (© 2022. The Society for Surgery of the Alimentary Tract.)

Background: We described trends and disparities in utilization of systemic chemotherapy in metastatic hepato-pancreato-biliary (HPB) cancers., Methods: We queried the National Cancer Database for metastatic HPB cancers [hepatocellular carcinoma (HCC), biliary tract cancers (BTC), pancreatic adenocarcinoma (PDAC)]. We used multivariable analysis to examine the factors associated with utilization of systemic chemotherapy. We utilized marginal structural logistic models to estimate the effect of health insurance, facility type, or facility volume on utilization of systemic chemotherapy., Results: We identified 162,283 patients with metastatic HPB cancers: 23,923 (14.7%) had HCC, 26,766 (16.5%) had BTC, and 111,594 (68.8%) had PDAC. A total of 37.2% patients with HCC, 55.6% with BTC, and 56.4% with PDAC received chemotherapy. Age ≥70 years and Charlson-Deyo score ≥2 were associated with lower likelihood of receiving chemotherapy across all cancers. Patients with private health insurance had higher receipt of chemotherapy. Receiving treatment at academic facilities had no effect on the receipt of chemotherapy. Treatment of patients with HCC or PDAC at high-volume facilities resulted in higher receipt of chemotherapy., Conclusion: A significant proportion of patients with metastatic HPB cancers do not receive systemic chemotherapy. Several disparities in administration of chemotherapy for metastatic HPB cancers exist., (Copyright © 2022 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Background: Surgical volume-outcome relationships have been described for a variety of procedures. There is scant literature on total institutional volume and outcomes in patients who are nonoperatively managed. We examined the average treatment effect of total hepatopancreatobiliary malignancy case volume on survival outcomes of patients with nonresected hepatobiliary malignancies., Methods: We identified patients with hepatopancreatobiliary malignancies [pancreatic adenocarcinoma, pancreatic neuroendocrine neoplasms, hepatocellular carcinoma, biliary tract cancers] within the National Cancer Database (2004-2018). We determined percentile thresholds based on the total annual hepatopancreatobiliary malignancy case volume. We then identified nonoperatively managed patients with hepatocellular carcinoma or biliary tract cancers. We used inverse probability-weighted Cox regression to estimate the effect of facility volume on overall survival., Results: We identified 710,988 patients with hepatopancreatobiliary malignancies. Total annual hepatopancreatobiliary malignancy case volume of 32, 71, and 177 cases/year corresponded to the 25th, 50th, and 75th percentiles. A total of 96,420 with hepatocellular carcinoma and 52,627 patients with biliary tract cancers were managed nonoperatively. In patients with hepatocellular carcinoma or biliary tract cancer, treatment at ≥25th, ≥50th, and ≥75th percentile facilities was associated with improved median, 1-, 2-, and 3-year overall survival compared with treatment at lower-percentile facilities. On inverse probability-weighted Cox analysis, treatment at higher-percentile facilities resulted in a lower hazard of death. Consistent findings were observed in patients with early or intermediate/advanced hepatocellular carcinoma or metastatic biliary tract cancers., Conclusion: Patients with nonoperatively managed hepatocellular carcinoma or biliary tract cancer who receive treatment at higher-volume facilities have improved survival outcomes. These data suggest regionalization of care for patients with hepatocellular carcinoma or biliary tract cancer to high-volume centers may improve survival., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Surgical resection improves survival for patients with isolated colorectal liver metastasis. National studies on the disparities related to this topic are limited; therefore, we investigated factors that affect surgical treatment and survival., Methods: We queried the National Cancer Database (2010-2017) for patients with isolated synchronous colorectal liver metastasis. Multivariable logistic regression and Cox proportional hazard regressions were used to identify factors associated with surgical resection, treatment at high-volume facilities, and overall survival., Results: Of 34,050 patients with isolated colorectal liver metastasis, surgical resection (n = 7,810; 23.0%) was more likely among patients who were of high socioeconomic status (odds ratio = 1.16; 95% confidence interval, 1.04-1.31), traveled long distance for treatment (odds ratio = 1.48; 95% confidence interval, 1.31-1.66), and were treated at high-volume facilities (odds ratio = 4.86; 95% confidence interval, 14.45-5.30). Black patients were less likely to undergo resection (odds ratio = 0.75; 95% confidence interval, 0.69-0.82). Treatment at high-volume facility was more common among patients who were Black (odds ratio = 1.14; 95% confidence interval, 1.07-1.21), were of high socioeconomic status (socioeconomic status index 7: odds ratio = 1.21; 95% confidence interval, 1.11-1.31), and traveled long distance (odds ratio = 4.03; 95% confidence interval, 3.63-4.48) and less likely for nonmetropolitan residents and those of low socioeconomic status (P < .05). Patients of high socioeconomic status and those who traveled long distance, were treated at high-volume facilities, underwent surgical resection, and received perioperative chemotherapy had an associated survival advantage (P < .05 for all), whereas Black race was associated with poorer overall survival (P < .05)., Conclusion: Nonmedical patient factors, such as race, socioeconomic status, and geography, are associated with treatment and survival for isolated colorectal liver metastases. Disparities persist after adjusting for surgical resection and treatment facility. These barriers must be addressed to improve care for vulnerable cancer patients., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: To examine the average treatment effect of hepato-pancreato-biliary (HPB) cancer volume on survival outcomes of patients with non-resected pancreatic adenocarcinoma (PDAC)., Methods: We queried the National Cancer Database (2004-2018) for patients with HPB malignancies (PDAC, pancreatic neuroendocrine neoplasms, hepatocellular carcinoma, biliary tract cancers). We determined the 25th, 50th, and 75th percentiles based on the total annual HPB volume. We then identified patients with non-resected PDAC. We utilized inverse probability (IP)-weighted Cox regression to estimate the effect of facility volume on overall survival (OS)., Results: We identified 710,988 patients with HPB malignancies. The 25th, 50th, and 75th percentiles of total annual HPB volume were 32, 71, and 177 cases/year, respectively. We included a total of 196,150 patients with non-resected PDAC. Patients treated at ≥25th, ≥50th, and ≥75th percentile facilities had improved median OS compared to those treated at facilities below these thresholds (5.8 vs. 4.2months, 6.5 vs. 4.5months, 7.5 vs. 4.8months, respectively; p < 0.001 for all). Treatment at facilities ≥25th, ≥50th, and ≥75th percentile resulted in lower hazards of death than treatment at lower-percentile facilities (HR: 0.87, 95% CI: 0.84-0.90; HR: 0.87, 95% CI: 0.83-0.91; HR: 0.85, 95% CI: 0.79-0.91, respectively)., Conclusion: Our data suggest that consolidation of care of patients with PDAC to high-volume centers may be beneficial even in the nonoperative setting., (Copyright © 2022. Published by Elsevier Ltd.)

Introduction: Regardless of its rarity, and indolent clinical course, chest wall tumor places high morbidity and burden on patients especially when invasion to a neighboring structure is found. Once detected, surgery is the cornerstone for treatment of such etiology combined with chemo-radiotherapy. In order to maintain intact respiratory function, chest wall reconstruction must be performed whenever resection is done. Herein, we present a case of chest wall tumor that necessitated three ribs and part of hemidiaphragm resection and reconstruction with optimal post-operative results., Case Presentation: A 27-year-old male patient who had chest wall and diaphragm reconstruction for a chest wall Ewing sarcoma, using a single patch of expanded polytetrafluoroethylene (ePTFE) mesh with diaphragm implanted into the middle of the mesh. There were no immediate nor post-operative complications. The patient received post-operative radiotherapy with good functional and cosmetic results., Conclusion: We present a novel and safe technique for combined chest wall and diaphragmatic resection following excision of an invading tumor while ensuring cosmesis and functionality of the ribcage as well as the diaphragm., (© 2021. The Author(s).)

Background: The open approach to right hemicolectomy remains the most widely adopted, whereas laparoscopic surgery is technically more demanding with possible loss of benefit for lengthy procedures compared with open surgery. The aim of this study is to compare the outcomes of the laparoscopic versus open surgery for right colon cancer resections., Materials and Methods: Patients who underwent an elective and potentially curative right colectomy for colon cancer between 2015 and 2019 were included and those who underwent emergency surgery, palliative resection, or cytoreductive surgery were excluded. Patients were randomly matched on 1:2 basis for age, disease stage, neoadjuvant chemotherapy, and extent of colectomy (right vs. extended right hemicolectomy, and additional major resection). The analysis was conducted on an intention-to-treat basis. The outcomes were reported as median (range) or percent as appropriate., Results: Among 160 patients, 18 were excluded. The final matching included 69 patients. The were no significant differences between the groups regarding patients' age and sex distribution, tumor size, and preoperative serum albumin and hemoglobin. There were 2 conversions (8.7%) to open surgery. Although the operating time for laparoscopic surgery was longer (200 vs. 140 min, P<0.001), it was associated with less blood loss (50 vs. 100 mL, P=0.001) and shorter primary and total hospital stay (4.1 vs. 6.0 days, P<0.001). There were no differences in the rates of severe complications (0% vs. 13%), reoperations (0% vs. 4.3%), readmissions (13% vs. 8.7%), mortality (0% vs. 2.2%), R0 resections (95.7% vs. 97.8%), and lymph node retrieval rate (28 in each group)., Conclusion: The laparoscopic approach to right colon resection for colon cancer is associated with less operative trauma and quicker recovery compared with open surgery and offers an equivalent oncologic resection., Competing Interests: The author declares no conflicts of interest., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: The superficial femoral-popliteal vein (SFPV) is a reliable conduit for aortoiliac, infrainguinal, and venous reconstructions. In this prospective study, we characterized the anatomic and physiologic changes in SFPV harvest limbs and their relationship to the development of late venous complications., Methods: Since 1990, we have studied 61 patients after harvest of 86 SFPVs at 6-month intervals with clinical examinations, lower-extremity venous duplex, and venous function tests. The CEAP system was used as a means of categorizing clinical changes., Results: Mean (+/- SEM) follow-up was 37 +/- 3 months. Less than one third of harvest limbs had edema without skin changes (C3). No patient had major chronic venous changes (C4 to C6) or venous claudication. There were no significant differences in limb measurements between harvest and non-harvest limbs, except in a subgroup of patients with unilateral harvest in which there was a small but significant (P =.046) increase in harvest limb thigh and calf circumference, compared with the opposite non-harvest limb. These clinical results were not affected by the presence or absence of an intact greater saphenous vein (GSV). Large, direct collaterals (4 to 6 mm in diameter) between the popliteal vein stump and profunda femoris vein (PFV) were seen by means of duplex ultrasonography in 29 harvest limbs (34%). The remainder appeared to have smaller, less direct collaterals to the PFV. Mild venous reflux with rapid cuff deflation was present at the popliteal or posterior tibial vein in nine of 79 harvest limbs (11%). Six of these nine limbs (67%) with reflux were clinical class C3, compared with only 19 of the 70 limbs without reflux (27%; P =.02). Ambulatory venous pressure (AVP) with exercise was significantly increased in harvest limbs (60 +/- 4.7 mm Hg), compared with non-harvest limbs (47.8 +/- 5.2 mm Hg; P =.049). The AVP recovery time of harvest limbs (14.0 +/- 1.0 seconds) was reduced, compared with non-harvest limbs (23.5 +/- 4.5 seconds; P =.02). AVPs (exercise) remained stable or decreased in six of 10 harvest limbs measured serially. Venous refill time in harvest limbs (15.1 +/- 1.1 seconds) was shortened, compared with non-harvest limbs (22.3 +/- 2. 1 seconds)(P =.002). Venous outflow obstruction measured by means of plethysmography was present in 93% of harvest limbs, compared with 36% of non-harvest limbs (P =.001)., Conclusion: SFPV harvest results in minimal mid-term to late-term lower-extremity venous morbidity despite outflow obstruction. The most likely mechanisms preserving clinical status include the low incidence of mild reflux, the presence of collateral venous channels, and the lack of progression in abnormal harvest limb physiology. The absence of the ipsilateral GSV does not adversely affect clinical outcome.

Purpose: The net benefit of routine intraoperative autotransfusion (IAT) in patients undergoing elective infrarenal aortic surgery was studied., Methods: One hundred patients undergoing abdominal aortic aneurysm (AAA) repair (n = 50) or aortofemoral bypass (AFB) for occlusive disease (n = 50) were randomized to IAT and control groups. This experience accounted for 58% of patients undergoing aortic surgery during the 16-month study period., Results: IAT and control groups were balanced for preoperative demographics, disease (50:50 split of AFB:AAA in each group), and risk factors. There were no significant differences between patients randomized to IAT and control patients in estimated blood loss (EBL), allogeneic blood transfusion (units administered intraoperatively, postoperatively, and total), proportion of patients not receiving allogeneic blood (34% of patients randomized to IAT and 28% of control patients), postoperative hemoglobin/hematocrit levels, and complications. IAT did not reduce allogeneic blood transfusion among all patients undergoing aortic surgery nor in any subgroups that might be more likely to benefit, such as those undergoing AAA repair, those with 1000 mL or more EBL, and those receiving larger volumes of IAT-processed blood., Conclusion: We could find no net benefit of IAT in patients undergoing elective, infrarenal aortic surgery.

Background and Purpose: A major gastrointestinal complication (GIC) after aortic surgery may be disastrous, but these complications have received scant attention. This study was performed to determine the risk factors, associated events, and outcomes for patients with GIC., Methods: We performed a secondary analysis of a prospective study that examined 120 consecutive patients who underwent transperitoneal aortic revascularization for aneurysmal or occlusive disease., Results: The following 29 GICs developed in 25 patients (21%) within 30 days of aortic surgery: paralytic ileus that required replacement of nasogastric tubes (n = 12), upper gastrointestinal bleeding (n = 5), Clostridium difficile enterocolitis (n = 5), acute cholecystitis (n = 2), mechanical obstruction (n = 2), ascites (n = 2), and colon ischemia (n = 1). Seven patients required operations for GICs after aortic revascularization. A comparison of patients with and without GICs showed no differences in the prevalence of risk factors, presence of mesenteric artery stenoses, coexisting medical illnesses, antecedent gastrointestinal history, operative indication, preoperative fluid administration, or duration of operation. However, patients with GICs had more intraoperative complications (P = .004), greater intraoperative blood loss (P = .02), and more fluids during the postoperative period (P = .008). The mean duration of mechanical ventilation was 71 +/- 23 hours for patients with GICs versus 7 +/- 2 hours for patients without GICs (P = .006). A higher prevalence of pulmonary (P = .004) and renal (P = .001) complications was seen in the patients with GICs. The mean stay in the intensive care unit was 16 +/- 2 days for patients with GICs as compared with 5 +/- 0.4 days for patients without GICs (P < .001). Four deaths occurred, all caused by multisystem organ failure: 3 patients had GICs, and 1 did not have a GIC (P = .007)., Conclusions: These results show that GICs are prevalent in transperitoneal aortic surgery and are associated with severe morbidity rates, increased hospital costs because of prolonged stay, and increased mortality rates. Some GICs appear to be associated with intraoperative events that lead to visceral hypoperfusion, and others can be attributed to mechanical causes. However, none of the variables examined in this study were predictive of GICs. In all, GICs should be considered serious adverse sequela after aortic revascularization. Because no risk factors for GICs have been identified, these complications currently cannot be prevented.

Purpose: To evaluate the routine use of pulmonary artery catheters (PAC) in patients who undergo aortic surgery., Methods: One hundred twenty patients were randomized to placement of PACs for perioperative monitoring and hemodynamic optimization (tune up) in the intensive care unit on the night before aortic operation, or to intravenous hydration in the ward and perioperative monitoring without PACs. Before randomization, all patients underwent routine adenosine thallium-201 scintigraphy., Results: To meet predetermined endpoints, 30 PAC patients (50%) received nitrates, inotropic agents, or both. PAC patients received more fluid in the preoperative period (p < 0.001) and in the first 24 hours after operation (p = 0.002) than control subjects. Eleven PAC patients (18%) and three control subjects (5%) had adverse intraoperative events (p = 0.02). There were 20 adverse postoperative events in 15 PAC patients (25%; nine cardiac, seven pulmonary, four acute tubular necrosis), which was not different compared with 11 postoperative events in 10 control subjects (17%; five cardiac, five pulmonary, one acute tubular necrosis). There were also no differences in duration of mechanical ventilation, intensive care unit stay, or hospital stay between groups. Postoperative cardiac complications were more common among patients who had a history of congestive heart failure (p = 0.02; odds ratio, 3.75; confidence interval, 1.3 to 11) or reperfusion defects on adenosine thallium scintigraphy (p = 0.01; odds ratio, 3.4; confidence interval, 1.2 to 9.4), regardless of group., Conclusions: Routine use of PACs for perioperative monitoring with the above protocol during aortic surgery is not beneficial and may be associated with a higher rate of intraoperative complications. Preoperative tune up does not prevent postoperative cardiac, renal, and other complications. Variables such as cardiac risk factors and adenosine thallium scintigraphy may be more important predictors of cardiac events in patients who undergo aortic operations.