An Age-Stratified Analysis of Early Postoperative Mortality Among Medicare-Eligible Patients With Common Gastrointestinal and Hepato-pancreato-biliary Malignancies.

Background: The frequency of major cancer surgery in the elderly (≥80 years) has increased concomitantly with the rise in average age of the population. We assessed early postoperative mortality following hepato-pancreato-biliary (HPB) and gastrointestinal (GI) procedures for common malignancies stratified by age. Methods: The National Cancer Database (2004-2017) was queried for patients who underwent resection for GI (gastroesophageal and colorectal) or HPB (pancreatic adenocarcinoma, biliary tract, and primary liver) cancers. We compared early postoperative mortality (30 d and 90 d) stratified by age (65-79 vs ≥80 years) and procedure, and compared survival outcomes by age and operative vs nonoperative management. Results: A total of 709,358 patients were included. The 30-day mortality ranged from 1.8% to 5.8% among patients 65-79 years and from 3.2% to 12.4% among patients ≥80 years depending on procedure. The 90-day mortality ranged from 3.6% to 10.6% in patients 65-79 years compared to 8.4%-21.0% among patients ≥80 years. The overall 90-day mortality was 5.2% for patients 65-79 years and 12.0% for patients ≥80 years (P < .001). Age ≥80 was associated with worse survival among operatively managed patients with each upper GI, HPB, and lower GI malignancy relative to younger patients on multivariable analysis. However, operative management of patients ≥80 years was associated with improved survival relative to nonoperative management. Discussion: Elderly patients suffer higher postoperative mortality after major GI and HPB cancer surgery, but operative management is associated with improved survival among patients ≥80 years as compared to nonoperative management. These data are important to contextualize when counseling elderly patients on their treatment options for localized GI and HPB cancers.

Comparison of Hospital Volume and Risk-Standardized Mortality Rate as a Proxy for Hospital Quality in Complex Oncologic Hepatopancreatobiliary Surgery.

BACKGROUND: Centralization of hepatopancreatobiliary procedures to more experienced centers has been recommended but remains controversial. Hospital volume and risk-stratified mortality rates (RSMR) are metrics for interhospital comparison. We compared facility operative volume with facility RSMR as a proxy for hospital quality. PATIENTS AND METHODS: Patients who underwent surgery for liver (LC), biliary tract (BTC), and pancreatic (PDAC) cancer were identified in the National Cancer Database (2004-2018). Hierarchical logistic regression was used to create facility-specific models for RSMR. Volume (high versus low) was determined by quintile. Performance (high versus low) was determined by RSMR tercile. Primary outcomes included median facility RSMR and RSMR distributions. Volume- and RSMR-based redistribution was simulated and compared for reductions in 90-day mortality. RESULTS: A total of 106,217 patients treated at 1282 facilities were included; 17,695 had LC, 23,075 had BTC, and 65,447 had PDAC. High-volume centers (HVC) had lower RSMR compared with medium-volume centers and low-volume centers for LC, BTC, and PDAC (all p < 0.001). High-performance centers (HPC) had lower RSMR compared with medium-performance centers and low-performance centers for LC, BTC, and PDAC (all p < 0.001). Volume-based redistribution required 16.0 patients for LC, 11.2 for BTC, and 14.9 for PDAC reassigned to 15, 22, and 20 centers, respectively, per life saved within each US census region. RSMR-based redistribution required 4.7 patients for LC, 4.2 for BTC, and 4.9 for PDAC reassigned to 316, 403, and 418 centers, respectively, per life saved within each US census region. CONCLUSIONS: HVC and HPC have the lowest overall and risk-standardized 90-day mortality after oncologic hepatopancreatobiliary procedures, but RSMR may outperform volume as a measure of hospital quality.

First-line Immunotherapy for Metastatic Merkel Cell Carcinoma: Analysis of Real-world Survival Data and Practice Patterns.

BACKGROUND: 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.

Creation and Implementation of an Online Tool for Feedback on Resident Teaching: A Pilot Study.

OBJECTIVE: There are few assessments of the competence and growth of surgical residents as educators. We developed and piloted an observation-based feedback tool (FT) to provide residents direct feedback during a specific teaching session, as perceived by medical students (MS). We hypothesized that residents' performance would improve with frequent, low stakes, observation-based feedback. SETTING: This prospective study took place at an academic general surgery program. PARTICIPANTS: Focus groups of MS, surgical residents, and faculty informed FT development. MS completed the FT regarding resident teaching. DESIGN: The FT utilized 5 slider-bar ratings (0 to 100) about the teaching encounter and a checklist of 16 desirable teaching behaviors. QR codes and weekly email links were distributed for 12 months (6 clerkship blocks) to promote use. Residents were sent their results after each block. A survey after each block assessed motivation for use and gathered feedback on the FT. Descriptive statistics were used for analysis (medians, IQRs). Primary measures of performance were median of the slider-bar scores and the number of teaching behaviors. RESULTS: The FT was used 111 times; 37 of 46 residents were rated by up to 65 MS. The median rating on the slider-bars was 100 and the median number of desirable teaching behaviors was 12; there were no differences based on gender or PGY level. 10 residents had 5 or more FT observations during the year. Four residents had evaluations completed in 4 or more blocks and 19 residents had evaluations completed in at least 2 blocks. Over time, 13 residents had consistent slider-bar scores, 1 resident had higher scores, and 5 residents had lower scores (defined as a more than 5-point change from initial rating). Frequency of use of the FT decreased over time (38, 32, 9, 21, 7, 5 uses per block). The post-use survey was completed by 24 MS and 19 residents. Most common reasons for usage were interest in improving surgical learning environment, giving positive feedback (MS), and improving teaching skills (residents). Most common reasons for lack of usage from residents were "I did not think I taught enough to ask for feedback," "I forgot it existed," and "I did not know it existed." CONCLUSIONS: The FT did not lead to any meaningful improvement in resident scores over the course of the year. This may be due to overall high scores, suggesting that the components of the FT may require reevaluation. Additionally, decreased utilization of the instrument over time made it challenging to assess change in performance of specific residents, likely due to lack of awareness of the FT despite frequent reminders. Successful implementation of observation-based teaching assessments may require better integration with residency or clerkship objectives.

Outcomes of Hepatic Artery-Based Therapies and Systemic Multiagent Chemotherapy in Unresectable Colorectal Liver Metastases: A Systematic Review and Meta-analysis.

BACKGROUND: Treatment of unresectable colorectal liver metastases (UCRLM) includes locoregional and systemic therapy. A comprehensive analysis capturing long-term outcomes of these treatment options has not been performed. OBJECTIVE: A systematic review and meta-analysis was performed to calculate pooled outcomes of hepatic artery infusion with systemic chemotherapy (HAI-S), transarterial chemoembolization with systemic chemotherapy (TACE-S), transarterial radioembolization with systemic chemotherapy (TARE-S), doublet (FOLFOX, FOLFIRI), and triplet chemotherapy (FOLFOXIRI). METHODS: Outcomes included overall survival (OS), progression-free survival (PFS), rate of conversion to resection (CTR), and response rate (RR). RESULTS: A total of 32, 7, 9, and 14 publications were included in the HAI-S, TACE-S, and TARE-S chemotherapy arms. The 6/12/24/36-month OS estimates for HAI-S, TACE-S, TARE-S, FOLFOX, FOLFIRI, and FOLFOXIRI were 97%/80%/54%/35%, 100%/83%/40%/14%, 82%/61%/34%/21%, 96%/83%/53%/36%, and 96%/93%/72%/55%. Similarly, the 6/12/24/36-month PFS estimates were 74%/44%/19%/14%, 66%/20%/9%/3%, 57%/23%/10%/3%, 69%/30%/12%/7%, and 88%/55%/18%/11%. The corresponding CTR and RR rates were 31, 20%, unmeasurable (TARE-S), 35, 53; and 49, 45, 45, 50, 80%, respectively. The majority of chemotherapy studies included first-line therapy and liver-only metastases, whereas most HAI-S studies were pretreated. On subgroup analysis in first-line setting with liver-only metastases, the HAI-S arm had comparable outcomes to FOLFOXIRI and outperformed doublet chemotherapy regimens. Although triplet chemotherapy appeared to outperform other arms, high toxicity and inclusion of potentially resectable patients must be considered while interpreting results. CONCLUSIONS: HAI-S and multiagent chemotherapy are effective therapies for UCRLM. To make definitive conclusions, a randomized trial with comparable patient characteristics and line of therapy will be required. The upcoming EA2222 PUMP trial may help to address this question.

Risk factors of developing nonalcoholic fatty liver disease after pancreatic resection: a systematic review and meta-analysis.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) occurs in 10% to 40% of patients after pancreatic resection. Pancreatic exocrine insufficiency (PEI) is thought to be closely associated with NAFLD; however, the mechanism of NAFLD is not clearly understood. We perform a systematic review and meta-analysis to better understand the risk factors of NAFLD. METHODS: A systematic literature search was performed in the MEDLINE database. Studies focused on the risk factors associated with NAFLD in patients undergoing pancreatectomy. The odds ratios (ORs) denoting the association of risk factors with NAFLD after resection were curated. RESULTS: Of 814 published articles, 26 studies met the inclusion criteria. Combined, these studies included clinical data on 4055 patients. The pooled incidence of NAFLD was 29% (23%-35%). Among the various risk factors analyzed, the following had a significant likelihood of NAFLD on forest plot analysis: female gender (OR, 2.44), pancreatic ductal adenocarcinoma (OR, 2.11), portal vein or superior mesenteric vein resection (OR, 1.99), dissection of nerve plexus around the superior mesenteric artery (OR, 1.93), and adjuvant chemotherapy (OR, 1.58). Only 2 studies investigated 2 different measurements of quantitative PEI, which could not be used for analysis. Owing to heterogeneity of studies, pancreatic remanent volume, which is considered a marker for PEI could not be evaluated. Pancreatic enzyme replacement therapy (PERT) was not associated with NAFLD. CONCLUSION: Numerous factors are associated with NAFLD after pancreatectomy. Previous research shows that PEI may be associated with NAFLD; however, this could not be compared in our meta-analysis. Further research is required to study the role of PERT in NAFLD.

Eliminating Hands-Off Handoffs: Improvement in Perioperative Handoff Communication With a Multidisciplinary Tool Initiative.

INTRODUCTION: Handoffs between the operating room (OR) and post-anesthesia care unit (PACU) require a high volume and quality of information to be transferred. This study aimed to improve perioperative communication with a handoff tool. METHODS: Perioperative staff at a quaternary care center was surveyed regarding perception of handoff quality, and OR to PACU handoffs were observed for structured criteria. A 25-item tool was implemented, and handoffs were similarly observed. Staff was then again surveyed. A multidisciplinary team led this initiative as a collaboration. RESULTS: After implementation, nursing reported improved perception of time spent (2.63-3.68, p = .02) and amount of information discussed (2.85-3.73, p = .05). Anesthesia also reported improved personal communication (3.69-4.43, p = .004), effectiveness of handoffs (3.43-3.82, p = .02), and amount of information discussed (4.26-4.76, p = .05). After implementation, observed patient information discussed during handoffs increased for both surgical and anesthesia team members. The frequency of complete and near-complete handoffs increased (40%-74%, p < .001). CONCLUSIONS: A structured handoff tool increased the amount of essential information reported during handoffs between the OR and PACU and increased team members' perception of handoffs.

Understanding surgical attrition for "resectable" pancreatic cancer.

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.

Extended antibiotic therapy is associated with a lower rate of clinically relevant postoperative pancreatic fistula after pancreatoduodenectomy in intermediate- and high-risk patients: A single-institution analysis.

BACKGROUND: Clinically relevant postoperative pancreatic fistula remains a common complication after pancreatoduodenectomy. The fistula risk score is a validated tool to predict the risk of clinically relevant postoperative pancreatic fistula. To mitigate complications, we have implemented an extended antibiotic pathway for patients at increased risk of clinically relevant postoperative pancreatic fistula (fistula risk score ≥3). We report outcomes after pancreatoduodenectomy in patients at increased risk for clinically relevant postoperative pancreatic fistula who received extended antibiotic therapy compared to those who received standard perioperative antibiotics (single dose before incision). METHODS: Single-institution analysis of 87 patients who underwent elective pancreatoduodenectomy (2018-2022) with soft gland texture and fistula risk score ≥3 and were treated with (n = 34) or without (n = 53) 10 days of broad-spectrum antibiotics (piperacillin/tazobactam converted to amoxicillin/clavulanic acid at discharge) after surgery. Associations between extended antibiotics and postoperative outcomes were analyzed. RESULTS: Baseline clinicodemographic factors were similar between cohorts. Patients who received extended antibiotics had shorter index days (6 vs 8 days, P = .004) and 90-day composite length of stay (8.5 vs 12 days, P = .018). Patients who received extended antibiotics had lower rates of clinically relevant postoperative pancreatic fistula (11.8% vs 37.7%; odds ratio = 0.17, 95% confidence interval: 0.04-0.68), wound infections (8.8% vs 30.2%; odds ratio = 0.08, 95% confidence interval: 0.01-0.50), organ space infections (14.7% vs 43.4%; odds ratio = 0.15, 95% confidence interval: 0.04-0.52), and image-guided drain placement (8.8% vs 34.0%; odds ratio = 0.15, 95% confidence interval: 0.04-0.62). There were no Clostridium difficile infections in the extended antibiotic group. CONCLUSION: Extended antibiotic therapy is associated with a lower rate of clinically relevant postoperative pancreatic fistula and associated complications after pancreatoduodenectomy in patients with a fistula risk score ≥3. These results form the basis of a randomized controlled trial (NCT05753735).

Preoperative therapy in melanoma: Evolving perspectives in clinical trials.

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.

Development of a Competency Framework Defining Effective Surgical Educators.

OBJECTIVE: The objective of this study is to develop a practical framework of competencies and behaviors which define an effective surgical educator. DESIGN: A modified Delphi approach was used. A literature review and series of discussions with surgical education experts led to creation of a survey instrument which was sent to surgical faculty and trainees from a single academic institution. The results from this initial survey informed the creation of the subsequent survey instrument which was also sent to surgical faculty and trainees. Focus groups with surgical faculty and residents were conducted separately, transcribed, deidentified, and then evaluated for recurring themes. A competency framework was developed. SETTING: The surveys were administered and focus groups were conducted at the University Hospitals Cleveland Medical Center, a tertiary care academic institution. PARTICIPANTS: Residents, fellows, and faculty surgeons from the fields of general surgery, plastic surgery, vascular surgery, orthopedic surgery, otolaryngology, neurosurgery, and urology. RESULTS: There were 115 responses (31.3%) from 367 faculty surgeons, residents, and fellows invited to complete the initial survey examining 50 competencies. Eighteen competencies received a mean Likert score of at least 4 by both faculty and residents and were included in the subsequent survey instrument which was completed by 72 participants (19.6%). Focus groups were held separately with 6 faculty surgeons and 6 residents. Analysis of the survey results and focus group discussions identified several themes which informed the development of a competency framework consisting of 5 overarching competencies as well as 16 specific behaviors. CONCLUSIONS: A practical framework was developed consisting of 5 competencies and 16 behaviors which define an effective surgical educator. The 5 competencies are: 1) fosters psychological safety, 2) displays exemplary medical knowledge and patient care, 3) diagnoses the learner and adjusts teaching, 4) communicates thought process to trainee, and 5) displays learner-centeredness. Based on the competency framework, residency leadership may specifically tailor faculty development initiatives to improve surgical education programming.

Surgical Resection Alone is Associated With Higher Long-Term Survival Than Multiagent Chemotherapy Alone for Patients With Localized Biliary Tract Cancers.

INTRODUCTION: We compared long-term survival of patients with localized biliary tract cancers (BTCs) treated with either surgical resection or multiagent chemotherapy. METHODS: Patients with localized BTC [gallbladder adenocarcinoma, extrahepatic cholangiocarcinoma, intrahepatic cholangiocarcinoma] were identified within the National Cancer Database (2010-2017). Piecewise-constant hazard modeling was used to estimate hazard ratios (HRs) at prespecified intervals: 0-30 d, 31-60 d, 61-90 d, and >90 d post-treatment. RESULTS: A total of 5988 patients with localized BTC were identified: 2697 (45.0%) received multiagent chemotherapy and 3291 (55.0%) underwent surgical resection. Patients with gallbladder adenocarcinoma or extrahepatic cholangiocarcinoma who were treated with surgical resection had an associated decline in overall survival (OS) as compared to those treated with multiagent chemotherapy within 0-30 d of treatment initiation (gallbladder adenocarcinoma [adjusted HR = 3.94, 95% confidence interval [CI]: 1.77-8.80]; extrahepatic cholangiocarcinoma [adjusted HR = 4.88, 95% CI: 2.76-8.61]). However, there was an associated improvement in OS for patients treated with surgical resection after 90 d from treatment initiation (gallbladder adenocarcinoma [adjusted HR = 0.36, 95% CI: 0.28-0.46]; extrahepatic cholangiocarcinoma [adjusted HR = 0.27, 95% CI: 0.24-0.32]). Among patients with intrahepatic cholangiocarcinoma, those who underwent surgical resection had an associated improvement in OS at 31-60 d (adjusted HR = 0.63, 95% CI: 0.40-0.99) and a further associated increase in OS at 61-90 d (adjusted HR = 0.34, 95% CI: 0.21-0.54) and after 90 d (HR = 0.23, 95% CI: 0.21-0.27) of treatment initiation. CONCLUSIONS: For patients with localized BTC, surgical resection alone is associated with improved long-term survival outcomes compared to multiagent chemotherapy alone.

Differences in the surgical management of early-stage hepatocellular carcinoma at minority versus non-minority-serving hospitals.

BACKGROUND: We examined differences in surgical intervention at minority-serving hospitals versus non-minority-serving hospitals among patients with early-stage hepatocellular carcinoma. We also investigated associations between surgical management and overall survival, stratified by minority-serving hospital status. METHODS: Patients with early-stage hepatocellular carcinoma, defined as cT1, were identified within the National Cancer Database (2004-2018). The primary outcome was surgical intervention (resection, ablation, or transplantation). The proportion of minority (non-Hispanic Black or Hispanic) patients treated at each facility was determined, and hospitals in the top decile were considered minority-serving hospitals. RESULTS: A total of 46,703 patients with early-stage hepatocellular carcinoma were identified, of whom 4,214 (9.0%) were treated at minority-serving hospitals. Patients treated at minority-serving hospitals were less likely to undergo surgical intervention than patients treated at non-minority-serving hospitals (odds ratio = 0.87, 95% confidence interval: 0.81-0.94). Minority patients treated at non-minority-serving hospitals were less likely to undergo surgical intervention than White patients (odds ratio = 0.86, 95% confidence interval: 0.82-0.90) and had a further associated decrease in the likelihood of surgical intervention when treated at minority-serving hospitals (odds ratio = 0.81, 95% confidence interval: 0.69-0.94). Regardless of minority-serving hospital status, surgery was associated with improved overall survival. There were no clinically meaningful differences in overall survival between White and minority patients who underwent surgery either at minority-serving hospitals or non-minority-serving hospitals. CONCLUSIONS: Patients with early-stage hepatocellular carcinoma had an associated decrease in the likelihood of surgical intervention when treated at minority-serving hospitals. Minority patients treated at minority-serving hospitals had an associated decrease in the likelihood of surgery, but to a lesser extent when treated at non-minority-serving hospitals. Surgery was associated with improved overall survival regardless of minority or minority-serving hospital status.

Disparities in guideline-compliant care for patients with pancreatic ductal adenocarcinoma at minority-versus non-minority-serving hospitals.

BACKGROUND: We examined disparities in guideline-compliant care at minority-serving hospitals (MSH) versus non-MSH among patients with localized or metastatic pancreatic adenocarcinoma (PDAC). METHODS: Patients with PDAC were identified within the National Cancer Database (2004-2018). Guideline-compliant care was defined as surgery + chemotherapy ± radiation therapy for localized and chemotherapy for metastatic disease. Facilities in the top decile of minority patients treated were considered MSH. RESULTS: A total of 190,950 patients were identified and most (59.6%) had metastatic disease. Overall, 6.4% of patients with localized and 8.2% of patients with metastatic disease were treated at MSH. Patients treated at MSH were less likely to receive guideline-compliant care (localized: OR = 0.78, 95% CI: 0.67-0.91; metastatic: OR = 0.77, 95% CI: 0.67-0.88). Minority patients were less likely to receive guideline-compliant care at non-MSH (localized: OR = 0.71, 95% CI: 0.67-0.75; metastatic: OR = 0.85, 95% CI: 0.82-0.89) or MSH (localized: OR = 0.85, 95% CI: 0.74-0.98; metastatic: OR = 0.91, 95% CI: 0.82-0.99). Patients treated at non-MSH or MSH who received guideline-compliant care were more likely to have higher OS regardless of stage or race. CONCLUSIONS: MSH patients were less likely to receive guideline-compliant care and minority patients were less likely to receive guideline-compliant care regardless of MSH status. Guideline-compliant care was associated with improved OS.

Trends in and Prognostic Significance of Time to Treatment in Pancreatic Cancer: A Population-Based Study.

INTRODUCTION: The association of time to treatment (TTT) with survival remains unclear in pancreatic adenocarcinoma (PDAC). In this study, we evaluate the recent trends in TTT, causes for delay, and its effect on survival. METHODS: We included patients with PDAC of all stages from the National Cancer Database (2004-2020) who underwent either surgery or chemotherapy/radiotherapy (CT/RT). TTT was defined as the duration between tissue diagnosis and first treatment. Linear regression (ß) was used to study the temporal trends in time delay. RESULTS: A total of 239,638 patients were included. The median TTT was 25 days. Using multivariable analysis, we found that increasing age (OR 1.48), female gender (OR 1.04), Black race (OR 1.3), lower educational status (OR 1.2), Medicaid, Medicare insurance, and uninsured (OR 1.2, 1.5, and 1.2, respectively), treatment at academic centers (OR 1.3), higher Charlson-Deyo comorbidity index (OR 1.2), and CT/RT (OR 1.5) were associated with increased TTT. There was a steady rise in median TTT from 21 to 28 days between 2004 and 2020 (ß = 0.3), suggestive of a worsening trend. Concurrently, there was an increasing trend in utilization of neoadjuvant CT/RT between 2004 and 2020 in early-stage PDAC. On Cox regression, TTT delay was associated with poor overall survival in stage I-IV patients (HR 1.1, 1.1, 1.09, and 1.53, respectively). CONCLUSIONS: Delayed treatment approaching 2 months was observed in 10% of the population. The rising temporal trend in TTT may be attributed to the increasing shift toward neoadjuvant CT/RT in early-stage PDAC and/or the increasing use of tissue biopsy prior to surgery.

Predictors of sentinel lymph node metastasis in very thin invasive melanomas.

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.

Discordance Between Conventional and Detailed Lymph Node Analysis in Resected, Node-negative Pancreatic or Ampullary Adenocarcinomas and Association With Adverse Survival Outcomes: A Single-institution Analysis.

OBJECTIVE: To assess the frequency of occult metastases (OM) in patients with resected pancreatic ductal adenocarcinoma (PDAC) or ampullary adenocarcinoma (AA) discovered on detailed pathologic examination on lymph nodes (LNs) previously considered negative by conventional analysis and to examine the association between OM and overall survival (OS). BACKGROUND: Poor prognosis of patients with no pathologic evidence of LN metastases may be due to OM that is not detected on conventional LN analysis. METHODS: Patients with LN-negative resected PDAC or AA (2010-2020) were identified from our institutional database. Original hematoxylin and eosin ( H and E ) slides were reanalyzed. In addition, selected LN were analyzed by H and E (3 sections/LN) and pan-cytokeratin (AE1-AE3/PCK26) immunohistochemistry. RESULTS: A total of 598 LNs from 74 LN-negative patients were reexamined. Nineteen patients (25.7%) had OM; 9 (47.4%) were found with immunohistochemistry but not on H and E . The number of positive LNs ranged from 1 to 3. No clinicodemographic, pathologic, or treatment-related factors were associated with OM. On conventional LN analysis, 3/19 patients (15.8%) had stage IA, 9/34 (26.5%) had stage IB, and 7/19 (36.8%) had stage IIA. On detailed LN analysis, 11/19 patients (57.9%) were upstaged to IIB, whereas 8/19 (42.1%) had isolated tumor cells only (N0i+). OM was associated with shorter OS (median OS: 22.3 vs 50.5 months; hazard ratio=3.95, 95% CI: 1.58-9.86). CONCLUSIONS: There is a 26% discordance rate between conventional and detailed LN pathologic analysis in resected PDAC and AA. The presence of OM is associated with shorter OS.