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Advances in intraoperative molecular imaging (IMI) may improve surgical outcomes when resecting tumors in the lung. A single-center trial was conducted using VGT-309, a cathepsin-targeted near-infrared imaging agent that causes lung nodules to fluoresce during surgical resection. The end point of this phase 2 study was to evaluate the frequency that IMI with VGT-309 resulted in a clinically significant event (CSE): localization of pulmonary nodules, discovery of unsuspected additional cancers, or identification of positive margins. Patients undergoing surgical resection for known or suspected cancer in the lung received VGT-309 (0.32 mg/kg) preoperatively. During the surgical procedure, localization and resection of the nodules were performed using standard surgical techniques. Near-infrared imaging was then used to localize nodules, seek occult lesions, and assess resection margins. Efficacy was measured by the frequency of CSEs. Of the 40 patients who underwent pulmonary resection with VGT-309, 17 (42.5%) had at least 1 CSE. Near-infrared imaging identified lesions not found by standard surgical methods in 16 patients, additional cancers not found by preoperative imaging in 1 patient, and margins within 5 mm of the closest staple line in 2 patients. VGT-309 performance was tested across a broad range of tumor types and commercial near-infrared imaging systems. VGT-309 appeared safe, well-tolerated, with no infusion reactions, and no drug-related serious adverse events. This phase 2 study demonstrated the utility of IMI with VGT-309 in localizing pulmonary nodules, recognizing synchronous lesions, and identifying positive margins. A multi-institutional study will further evaluate the efficacy of VGT-309. [ABSTRACT FROM AUTHOR]

Small animal models remain invaluable for the preclinical study of emerging molecular imaging agents. However, the data obtained in this setting are generated in genetically homogenous animals that do not mimic human pathophysiology. The purpose of this study was to prospectively validate precision-cut lung slices (PCLSs) obtained from patients with lung cancer as a translational tool for the development of targeted fluorophores. The lung tissue was gently inflated with 2% Low-Melt Agarose (Fisher, 16520050) to avoid lung damage and minimize inflation pressure. The slices were then loaded into specialized cylindrical cartridges and inserted into a compressotome, and slices 150 to 350 μm thick were cut. Samples were incubated with fluorophore conjugates for ex vivo validation and immunohistochemical staining for receptor expression. A total of 184 unique 3-dimensional, architecturally preserved normal lung and non-small cell lung cancer samples were obtained between 2020 and 2022. The median nodule size was 1.1 ± 0.21 cm for benign lesions and 2.1 ± 0.19 cm for malignant nodules. A total of 101 of 135 (74.8%) malignant lesions were adenocarcinoma spectrum lung cancers. The median viability was 9.78 ± 1.86 days, and 1 μM of FAPL-S0456 (high-affinity fibroblast activation protein [FAP] targeting ligand linked to the near-infrared fluorophore S0456, On Target Laboratories)–targeted near-infrared fluorochrome localization demonstrated correlative labeling of FAP-positive tumor areas with a correlation coefficient of +0.94 (P <.01). There was no FAP fluorochrome uptake in normal lungs (r = −1; P <.001). PCLSs comprise a novel human tissue–based translational model that can be used to validate the efficacy of molecular imaging fluorochromes. PCLSs preserve the tumor microenvironment and parenchymal architecture that closely resemble the interactions of the immune and stromal components in humans. [ABSTRACT FROM AUTHOR]

Pulmonary ground glass opacities (GGOs) are early-stage adenocarcinoma spectrum lesions that are not easily palpable. Challenges in localizing GGOs during intraoperative pathology can lead to imprecise diagnoses and additional time under anesthesia. To improve localization of GGOs during frozen section diagnosis, we evaluated a novel technique, 3-dimensional near-infrared specimen mapping (3D-NSM). Fifty-five patients with a cT1 GGO were enrolled and received a fluorescent tracer preoperatively. After resection, specimens were inspected to identify lesions. Palpable and nonpalpable nodules underwent 3D-NSM and the area of highest fluorescence was marked with a suture. Time for 3D-NSM, time for frozen section diagnosis, and number of tissue sections examined were recorded. To compare 3D-NSM with standard-of-care techniques, a control cohort of 20 subjects with identical inclusion criteria were enrolled. Specimens did not undergo 3D-NSM and were sent directly to pathology. 3D-NSM localized 54 of 55 lesions with 1 false negative. All 41 palpable lesions were identified by 3D-NSM. Thirteen (92.8%) of 14 nonpalpable lesions were located by 3D-NSM. Time to diagnosis for the 3D-NSM cohort was 23.5 minutes, compared with 26.0 minutes in the control cohort (P =.04). 3D-NSM did not affect time to diagnosis of palpable lesions (23.2 minutes vs 21.4 minutes; P =.10). 3D-NSM significantly reduced time to diagnosis for nonpalpable lesions (23.3 minutes vs 34.4 minutes; P <.0001). 3D-NSM also reduced the number of tissue sections analyzed in nonpalpable lesions (4.50 vs 11.00; P <.0001). 3D-NSM accurately localizes GGOs and expedites intraoperative diagnosis by reducing the number of tissue sections analyzed for nonpalpable GGOs. [Display omitted] [ABSTRACT FROM AUTHOR]

Xanthogranulomatous cholecystitis is a particularly destructive variant of cholecystitis marked by unique inflammatory changes evident in pathologic specimens. Multiple case series have evaluated this process. However, these often focus on differentiating it from malignancy and have largely been conducted in Asia, where the disease may differ from that seen in the Western hemisphere. This study evaluated surgical outcomes after cholecystectomy for xanthogranulomatous cholecystitis at a high-volume tertiary care institution in the United States. The goal was to determine whether the process can be identified preoperatively and whether modifications should be made to the operative approach in this setting. Patients with histopathological confirmation of xanthogranulomatous cholecystitis who underwent cholecystectomy between 2002 and 2019 were identified from an updated institutional database. Data regarding demographics, imaging findings, surgical procedures, and perioperative complications were reviewed retrospectively. A cohort of patients undergoing cholecystectomy for more typical diagnoses was also identified for comparison. Twenty-seven patients with a histopathologic diagnosis of xanthogranulomatous cholecystitis were identified. The median age was 64, and 17/27 (63.0%) were male. The majority of cases were done electively on patients admitted that day (17/27). Seventeen patients were evaluated with diagnostic ultrasonography, 21 with computed tomography scan, and 8 with magnetic resonance imaging; 21/27 patients had multiple modality studies. The most common singular finding was gallbladder wall thickening, but the radiographic findings were otherwise inconsistent. Twenty-five patients had planned laparoscopic cholecystectomies, but only 10 were completed. Only 8 of the 15 converted procedures were completed as simple cholecystectomies. Five patients required subtotal cholecystectomy. Median estimated blood loss was 250 cm3, and the median time of procedure was nearly 3 hours. Eight patients had complications, including 6 severe complications such as intraoperative bile duct injury. Xanthogranulomatous cholecystitis unfortunately has a nonspecific presentation, which can make it difficult to recognize preoperatively. It is to be suspected in cases featuring a distended, severely inflamed gallbladder that does not match the benign appearance of the patient. When the diagnosis is suspected, an open approach is justified and patients should be counseled as to the increased likelihood of atypical approaches and elevated risk of complication. Referral to a hepatobiliary specialist is to be considered. [ABSTRACT FROM AUTHOR]

Background: With increasing focus on health care quality and cost containment, volume-based referral strategies have been proposed to improve value in high-cost procedures, such as esophagectomy. While the effect of hospital volume on outcomes has been demonstrated, our goal was to evaluate the economic consequences of volume-based referral practices for esophagectomy.Methods: The nationwide inpatient sample (NIS) was queried for the years 2004-2013 for all patients undergoing esophagectomy. Patients were stratified by hospital volume quartile and substratified by preoperative risk and age. Clustered multivariable hierarchical logistic regression analysis was used to assess adjusted costs and mortality.Results: In total, 9270 patients were clustered based on annual hospital volume quartiles of < 7, 7 to 22, 23 to 87, and > 87 esophagectomies. After stratification by patient variables, high-volume centers performed esophagectomies in high-risk patients at the same cost as low-volume centers without significant difference in resource utilization. Overall, mortality decreased across volume quartiles (lowest 8.9 versus highest 3.6%, p < 0.0001). The greatest volume-mortality differences were observed among patients aged between 70 and 80 years (lowest 12.2 versus highest 6.2%, p = 0.009). Patients with high preoperative risk also derived mortality benefits with increasing hospital volume (lowest 17.5 versus highest 11.8%, p < 0.0001).Conclusions: This study demonstrates that the mortality improvements for high-risk patients undergoing esophagectomy at high-volume centers do not come at increased costs. These results suggest that health systems should consider selectively referring high-risk patients to high-volume centers within their region. [ABSTRACT FROM AUTHOR]

Background Experienced surgeons demonstrate improved pancreatoduodenectomy outcomes, but little is known about what distinguishes their practice. Furthermore, the concept of experience has been variably interpreted in the surgical literature. We investigated how 4 interpretations of experience influence pancreatoduodenectomy management decisions. Methods A survey assessing pancreatoduodenectomy practice patterns was distributed by 6 surgical societies. Regression analysis identified behaviors associated with 4 forms of experience: years in practice, surpassing the learning curve (≥50 pancreatoduodenectomies), high annual volume (≥25 pancreatoduodenectomy/year), and high career volume (>200 pancreatoduodenectomy). Results In the study, 861 surgeons responded, representing 6 continents. Senior surgeons were more likely to use pancreatogastrostomy, dunking/invagination, and external stents (all P < .05). Sixty-five percent of respondents surpassed the learning curve, and these surgeons were more likely to use a 2-layer pancreatic enteric anastomosis, stents, and the Fistula Risk Score (all P < .05). High annual volume surgeons were more likely to use the same reconstruction on every case and autologous tissue patches but less likely to use the Roux limb technique and multiple drains (all P < .05). High career volume surgeons mirrored the behaviors of those surpassing the learning curve except for using the Fistula Risk Score. Conclusion Experience encompasses several components, each of which seems to influence decision making in different ways. [ABSTRACT FROM AUTHOR]

Intraoperative molecular imaging (IMI) using tumor-targeted optical contrast agents can improve thoracic cancer resections. There are no large-scale studies to guide surgeons in patient selection or imaging agent choice. Here, we report our institutional experience with IMI for lung and pleural tumor resection in 500 patients over a decade. Between December 2011 and November 2021, patients with lung or pleural nodules undergoing resection were preoperatively infused with 1 of 4 optical contrast tracers: EC17, TumorGlow, pafolacianine, or SGM-101. Then, during resection, IMI was used to identify pulmonary nodules, confirm margins, and identify synchronous lesions. We retrospectively reviewed patient demographic data, lesion diagnoses, and IMI tumor-to-background ratios (TBRs). Five hundred patients underwent resection of 677 lesions. We found that there were 4 types of clinical utility of IMI: detection of positive margins (n = 32, 6.4% of patients), identification of residual disease after resection (n = 37, 7.4%), detection of synchronous cancers not predicted on preoperative imaging (n = 26, 5.2%), and minimally invasive localization of nonpalpable lesions (n = 101 lesions, 14.9%). Pafolacianine was most effective for adenocarcinoma-spectrum malignancies (mean TBR, 2.84), and TumorGlow was most effective for metastatic disease and mesothelioma (TBR, 3.1). False-negative fluorescence was primarily seen in mucinous adenocarcinomas (mean TBR, 1.8), heavy smokers (>30 pack years; TBR, 1.9), and tumors greater than 2.0 cm from the pleural surface (TBR, 1.3). IMI may be effective in improving resection of lung and pleural tumors. The choice of IMI tracer should vary by the surgical indication and the primary clinical challenge. [ABSTRACT FROM AUTHOR]

Background: There has been a proliferation of gastrointestinal surgical fellowships; however, little is known regarding their association with surgical volume and management approaches. Methods: Surveys were distributed to members of GI surgical societies. Responses were evaluated to define relationships between fellowship training and surgical practice with pancreatoduodenectomy (PD). Results: Surveys were completed by 889 surgeons, 84.1% of whom had completed fellowship training. Fellowship completion was associated with a primarily HPB or surgical oncology-focused practice (p < 0.001), and greater median annual PD volume (p = 0.030). Transplant and HPB fellowship-trained respondents were more likely to have high-volume (≥20) annual practice (p = 0.005 and 0.029, respectively). Regarding putative fistula mitigation strategies, HPB-trained surgeons were more likely to use stents, biologic sealants, and autologous tissue patches (p = 0.007, <0.001 and 0.001, respectively). Surgical oncology trainees reported greater autologous patch use (p = 0.003). HPB fellowship-trained surgeons were less likely to routinely use intraperitoneal drainage (p = 0.036) but more likely to utilize early (POD ≤ 3) drain amylase values to guide removal (p < 0.001). Finally, HPB fellowship-trained surgeons were more likely to use the Fistula Risk Score in their practice (29 vs. 21%, p = 0.008). Conclusion: Fellowship training correlated with significant differences in surgeon experience, operative approach, and use of available fistula mitigation strategies for PD. [ABSTRACT FROM AUTHOR]