80 Venous thromboembolism diagnosis definition in claims data: implications for research

OBJECTIVES/GOALS: Venous thromboembolism (VTE) is a major cause of morbidity and mortality. Due to its relatively low incidence, prospective studies are limited. This makes administrative claims a promising data source to study VTE. We sought to examine the reproducibility of results using different VTE definitions from the published literature. METHODS/STUDY POPULATION: We conducted a retrospective analysis of a random 10% sample of the 2010-2022 IQVIA LifeLink PharMetrics Plus™ database, an administrative claims database representative of the commercially insured population of the United States. We selected cancer patients undergoing major gastrointestinal surgery, who have a higher risk for postoperative VTE (deep venous thrombosis [DVT] and/or pulmonary embolism [PE]). VTE was defined using ICD-9-CM and ICD-10-CM codes using definitions from 4 individual published studies. We compared the 4 definitions with respect to the incidence of VTE and factors associated with post-discharge VTE using standard univariate and multivariable logistic regression models. The same logistic regression models were used for each of the 4 definitions. RESULTS/ANTICIPATED RESULTS: There were substantial differences in VTE coding among the 4 definitions (range 107 to 225 ICD-9/10 codes for DVT and 12 to 24 codes for PE). The eligible population comprised 2,360 patients (49% female) with a median age of 49 years (interquartile range 47-52 years). During the index surgery hospitalization, a total of 58, 62, 63, and 83 patients developed VTE using the 4 definitions. In the 2,126 patients eligible for VTE prophylaxis, a total of 108, 68, 73, and 107 patients developed post-discharge VTE (range for DVT 35 to 81, range for PE 39 to 76). On multivariable analysis, factors independently associated with VTE included age using 1 of 4 definitions, esophageal surgery type using 3 of 4 definitions, and liver surgery type and Elixhauser score using all 4 definitions. DISCUSSION/SIGNIFICANCE: The incidence of VTE is directly affected by differences in ICD-9/10 codes used. Definitions for important clinical outcomes should be standardized when using administrative claims data in order to improve reproducibility of findings

Predictors of sentinel lymph node metastasis in patients with thin melanoma: An international multi-institutional collaboration

Background: Consideration of sentinel lymph node biopsy (SLNB) is recommended for patients with T1b melanomas and T1a melanomas with high-risk features; however, the proportion of patients with actionable results is low. We aimed to identify factors predicting SLNB positivity in T1 melanomas by examining a multi-institutional international population. Methods: Data were extracted on patients with T1 cutaneous melanoma who underwent SLNB between 2005 and 2018 at five tertiary centers in Europe and Canada. Univariable and multivariable logistic regression analyses were performed to identify predictors of SLNB positivity. Results: Overall, 676 patients were analyzed. Most patients had one or more high-risk features: Breslow thickness 0.8–1 mm in 78.1% of patients, ulceration in 8.3%, mitotic rate > 1/mm2 in 42.5%, Clark’s level ≥ 4 in 34.3%, lymphovascular invasion in 1.4%, nodular histology in 2.9%, and absence of tumor-infiltrating lymphocytes in 14.4%. Fifty-three patients (7.8%) had a positive SLNB. Breslow thickness and mitotic rate independently predicted SLNB positivity. The odds of positive SLNB increased by 50% for each 0.1 mm increase in thickness past 0.7 mm (95% confidence interval [CI] 1.05–2.13) and by 22% for each mitosis per mm2 (95% CI 1.06–1.41). Patients who had one excised node (vs. two or more) were three times less likely to have a positive SLNB (3.6% vs. 9.6%; odds ratio 2.9 [1.3–7.7]). Conclusions: Our international multi-institutional data confirm that Breslow thickness and mitotic rate independently predict SLNB positivity in patients with T1 melanoma. Even within this highly selected population, the number needed to diagnose is 13:1 (7.8%), indicating that more work is required to identify additional predictors of sentinel node positivity

Enhancing Neoadjuvant Virotherapy’s Effectiveness by Targeting Stroma to Improve Resectability in Pancreatic Cancer

About one-fourth of patients with pancreatic ductal adenocarcinoma (PDAC) are categorized as borderline resectable (BR) or locally advanced (LA). Chemotherapy and radiation therapy have not yielded the anticipated outcomes in curing patients with BR/LA PDAC. The surgical resection of these tumors presents challenges owing to the unpredictability of the resection margin, involvement of vasculature with the tumor, the likelihood of occult metastasis, a higher ratio of positive lymph nodes, and the relatively larger size of tumor nodules. Oncolytic virotherapy has shown promising activity in preclinical PDAC models. Unfortunately, the desmoplastic stroma within the PDAC tumor microenvironment establishes a barrier, hindering the infiltration of oncolytic viruses and various therapeutic drugs—such as antibodies, adoptive cell therapy agents, and chemotherapeutic agents—in reaching the tumor site. Recently, a growing emphasis has been placed on targeting major acellular components of tumor stroma, such as hyaluronic acid and collagen, to enhance drug penetration. Oncolytic viruses can be engineered to express proteolytic enzymes that cleave hyaluronic acid and collagen into smaller polypeptides, thereby softening the desmoplastic stroma, ultimately leading to increased viral distribution along with increased oncolysis and subsequent tumor size regression. This approach may offer new possibilities to improve the resectability of patients diagnosed with BR and LA PDAC

Pancreatic surgery outcomes: multicentre prospective snapshot study in 67 countries

Background: Pancreatic surgery remains associated with high morbidity rates. Although postoperative mortality appears to have improved with specialization, the outcomes reported in the literature reflect the activity of highly specialized centres. The aim of this study was to evaluate the outcomes following pancreatic surgery worldwide.Methods: This was an international, prospective, multicentre, cross-sectional snapshot study of consecutive patients undergoing pancreatic operations worldwide in a 3-month interval in 2021. The primary outcome was postoperative mortality within 90 days of surgery. Multivariable logistic regression was used to explore relationships with Human Development Index (HDI) and other parameters.Results: A total of 4223 patients from 67 countries were analysed. A complication of any severity was detected in 68.7 percent of patients (2901 of 4223). Major complication rates (Clavien-Dindo grade at least IIIa) were 24, 18, and 27 percent, and mortality rates were 10, 5, and 5 per cent in low-to-middle-, high-, and very high-HDI countries respectively. The 90-day postoperative mortality rate was 5.4 per cent (229 of 4223) overall, but was significantly higher in the low-to-middle-HDI group (adjusted OR 2.88, 95 per cent c.i. 1.80 to 4.48). The overall failure-to-rescue rate was 21 percent; however, it was 41 per cent in low-to-middle-compared with 19 per cent in very high-HDI countries.Conclusion: Excess mortality in low-to-middle-HDI countries could be attributable to failure to rescue of patients from severe complications. The authors call for a collaborative response from international and regional associations of pancreatic surgeons to address management related to death from postoperative complications to tackle the global disparities in the outcomes of pancreatic surgery (NCT04652271; ISRCTN95140761)