Radiologic Occult Metastases in Pancreatic Cancer: Analysis of Risk Factors and Survival Outcomes in the Age of Contemporary Neoadjuvant Multi-agent Chemotherapy.

BACKGROUND: Radiologic occult metastatic disease (ROMD) in patients with pancreatic ductal adenocarcinoma (PDAC) who undergo contemporary neoadjuvant chemotherapy (NAC) has not been well studied. This study sought to analyze the incidence, risk factors, and oncologic outcomes for patients who underwent the NAC approach for PDAC. METHODS: A retrospective review analyzed a prospectively maintained database of patients who had potentially resectable PDAC treated with NAC and were offered pancreatectomy at our institution from 2011 to 2022. Multivariable regression analysis was performed to assess risk factors associated with ROMD. Kaplan-Meier curves with log-rank analyses were generated to estimate time-to-event end points. RESULTS: The study enrolled 366 patients. Upfront and borderline resectable anatomic staging comprised 80% of the cohort, whereas 20% had locally advanced disease. The most common NAC regimen was FOLFIRINOX (n = 274, 75%). For 55 patients (15%) who harbored ROMD, the most common site was liver-only metastases (n = 33, 60%). The independent risk factors for ROMD were increasing CA19-9 levels during NAC (odds ratio [OR], 7.01; confidence interval [CI], 1.97-24.96; p = 0.008), indeterminate liver lesions (OR, 2.19; CI, 1.09-4.39; p = 0.028), and enlarged para-aortic lymph nodes (OR, 6.87; CI, 2.07-22.74; p = 0.002) on preoperative cross-sectional imaging. Receipt of palliative chemotherapy (p < 0.001) and eventual formal pancreatectomy (p = 0.04) were associated with survival benefit in the log-rank analysis. The median overall survival (OS) of the patients with ROMD was nearly 15 months from the initial diagnosis, with radiologic evidence of metastases occurring after a median of 2 months. CONCLUSIONS: Radiologic occult metastatic disease remains a clinical challenge associated with poor outcomes for patients who have PDAC treated with multi-agent NAC.

Effect of Neoadjuvant Chemotherapy on Tumor-Infiltrating Lymphocytes in Resectable Gastric Cancer: Analysis from a Western Academic Center.

Tumor-infiltrating lymphocytes (TILs) are an emerging biomarker predictive of response to immunotherapy across a spectrum of solid organ malignancies. The characterization of TILs in gastric cancer (GC) treated with contemporary, multiagent neoadjuvant chemotherapy (NAC) is understudied. In this retrospective investigation, we analyzed the degree of infiltration, phenotype, and spatial distribution of TILs via immunohistochemistry within resected GC specimens treated with or without NAC at a Western center. We hypothesized that NAC executes immunostimulatory roles, as evidenced by an increased number of anti-tumor TILs in the tumor microenvironment. We found significantly elevated levels of conventional and memory CD8+ T cells, as well as total TILs (CD4+, CD8+, Treg, B cells), within chemotherapy-treated tumors compared with chemotherapy-naïve specimens. We also revealed important associations between survival and pathologic responses with enhanced TIL infiltration. Taken together, our findings advocate for an immunostimulatory role of chemotherapy and underscore the potential synergistic effect of combining chemotherapy with immunotherapy in resectable gastric cancer.

Group XIV C-type lectins: emerging targets in tumor angiogenesis.

C-type lectins, distinguished by a C-type lectin binding domain (CTLD), are an evolutionarily conserved superfamily of glycoproteins that are implicated in a broad range of physiologic processes. The group XIV subfamily of CTLDs are comprised of CD93, CD248/endosialin, CLEC14a, and thrombomodulin/CD141, and have important roles in creating and maintaining blood vessels, organizing extracellular matrix, and balancing pro- and anti-coagulative processes. As such, dysregulation in the expression and downstream signaling pathways of these proteins often lead to clinically relevant pathology. Recently, group XIV CTLDs have been shown to play significant roles in cancer progression, namely tumor angiogenesis and metastatic dissemination. Interest in therapeutically targeting tumor vasculature is increasing and the search for novel angiogenic targets is ongoing. Group XIV CTLDs have emerged as key moderators of tumor angiogenesis and metastasis, thus offering substantial therapeutic promise for the clinic. Herein, we review our current knowledge of group XIV CTLDs, discuss each's role in malignancy and associated potential therapeutic avenues, briefly discuss group XIV CTLDs in the context of two other relevant lectin families, and offer future direction in further elucidating mechanisms by which these proteins function and facilitate tumor growth.

Immune Landscape of Epstein-Barr Virus-Associated Gastric Cancer: Analysis From a Western Academic Institution.

INTRODUCTION: Epstein-Barr virus-associated gastric cancer (EBVaGC) may be a meaningful biomarker for potential benefit from immunotherapy. Further investigation is needed to characterize the immune landscape of EBVaGC. We assessed our institutional frequency of surgically treated EBVaGC and analyzed the immunologic biomarker profile and tumor-infiltrating lymphocyte (TIL) phenotypes of a series of EBVaGC compared to non-EBVaGC cases. METHODS: Available tissue samples from all patients with biopsy-confirmed gastric adenocarcinoma who underwent resection with curative intent from 2012 to 2020 at our institution were collected. In situ hybridization was used to assess EBV status; multiplex immunohistochemistry was performed to assess mismatch repair status, Programmed Death-Ligand 1 (PD-L1) expression, and phenotypic characterization of TILs. RESULTS: Sixty-eight samples were included in this study. EBVaGC was present in 3/68 (4%) patients. Among all patients, 27/68 (40%) had positive PD-L1 expression; two of three (67%) EBVaGC patients exhibited positive PD-L1 expression. Compared to non-EBVaGC, EBV-positive tumors showed 5-fold to 10-fold higher density of TILs in both tumor and stroma and substantially elevated CD8+ T cell to Tregulatory cell ratio. The memory subtypes of CD8+ and CD4+ T cells were upregulated in EBVaGC tumors and stromal tissue compared to non-EBVaGC. CONCLUSIONS: The incidence of surgically resected EBVaGC at our center was 4%. EBVaGC tumors harbor elevated levels of TILs, including memory subtypes, within both tumor and tumor-related stroma. Robust TIL presence and upregulated PD-L1 positivity in EBVaGC may portend promising responses to immunotherapy agents. Further investigation into routine EBV testing and TIL phenotype of patients with gastric cancer to predict response to immunotherapy may be warranted.

Atypical chemokine receptors: emerging therapeutic targets in cancer.

Atypical chemokine receptors (ACKRs) regulate the availability of chemokines via chemokine scavenging, while also having the capacity to elicit downstream function through ß-arrestin coupling. This contrasts with conventional chemokine receptors that directly elicit immune cell migration through G protein-coupled signaling. The significance of ACKRs in cancer biology has previously been poorly understood, but recent findings have highlighted the multifaceted role of these receptors in tumorigenesis and immune response modulation within the tumor microenvironment (TME). Additionally, recent research has expanded our understanding of the function of several receptors including GPR182, CCRL2, GPR1, PITPNM3, and C5aR2 that share similarities with the ACKR family. In this review, we discuss these recent developments, and highlight the opportunities and challenges of pharmacologically targeting ACKRs in cancer.

Lipoma and Its Doppelganger: The Atypical Lipomatous Tumor/Well-Differentiated Liposarcoma.

Lipomatous tumors are among the most common soft tissue lesions encountered by the general surgeon. Shared history and clinical presentation make differentiation between benign lipomas and low-grade liposarcomas a diagnostic dilemma. This article reviews the epidemiology, clinical history, diagnostic workup, management, natural history, and surveillance of benign lipomas and atypical lipomatous tumors/well-differentiated liposarcomas. Although it is important that aggressive, potentially malignant atypical lipomatous tumors and liposarcomas be managed in a multidisciplinary, preferably high-volume setting, it is equally as important for the nonspecialist general surgeon to be familiar with lipoma and its doppelganger-the well-differentiated liposarcoma.

Dynamic frailty: Objective physiological assessment to guide management in necrotizing pancreatitis.

BACKGROUND: Physical frailty as a measure of physiological reserve is an important yet understudied topic in necrotizing pancreatitis. We measured frailty metrics in patients with necrotizing pancreatitis at baseline and at 1 month to assess dynamic change. We hypothesized that greater baseline frailty and steeper decline in frailty biomarkers are associated with worse outcomes in necrotizing pancreatitis. METHODS: A retrospective analysis of an institutional, necrotizing pancreatitis-specific database was performed. First order outcomes were organ failure, infected necrosis, step-up approach failure, and mortality. Baseline frailty assessment included measurement of comorbid diseases (modified frailty index), nutritional status (prognostic nutritional index), and radiologic sarcopenia (psoas muscle index, Hounsfield unit average calculation). Dynamic frailty was evaluated using psoas muscle index and Hounsfield unit average calculation. Significant associations between baseline and dynamic frailty with outcomes were analyzed. RESULTS: Three hundred and forty-one patients were included in this study. Most patients were male (65%) with biliary etiology of necrotizing pancreatitis (46%). Baseline comorbid diseases and baseline sarcopenia were not associated with first order outcomes. Lower baseline prognostic nutritional index was associated with organ failure (P < .001) and infected necrosis (P < .001). After 30 days, 25% of patients became sarcopenic. Larger declines in all sarcopenia metrics were associated with organ failure, infected necrosis, and/or death (P < .05). Lower psoas area and density were independent risk factors for organ failure and infected necrosis. CONCLUSION: Dynamic changes in sarcopenia-focused frailty metrics were significantly and consistently associated with organ failure, infected necrosis, and death. Further development of a dynamic frailty index to objectively guide decision-making in necrotizing pancreatitis is warranted.

Use of primary surgical drains in synchronous resection for colorectal liver metastases: a NSQIP analysis of current practice paradigm.

BACKGROUND: There are no studies examining the use of subhepatic drains after simultaneous resection of synchronous colorectal liver metastases (sCRLM). This study aimed to (1) describe the current practices regarding primary drain placement, (2) evaluate drain efficacy in mitigating postoperative complications, and (3) determine impact of drain maintenance duration on patient outcomes. METHODS: The ACS-NSQIP targeted data from 2014 to 2017 were analyzed. Propensity score of surgical drain versus no drain cohorts was performed. Main study outcomes were mortality, major morbidity, organ/space surgical site infection (SSI), secondary drain/aspiration procedure, and any septic events. Additional univariate/multivariate logistic analyses were performed to identify associations with drain placement and duration. Major hepatectomy was defined as formal right hepatectomy and any trisectionectomy. RESULTS: 584 combined liver and colorectal resection (CRR) cases were identified. Open partial hepatectomy with colectomy was the most common procedure (70%, n = 407). Nearly 40% of patients received surgical drains (n = 226). Major hepatectomy, lower serum albumin, and no intraoperative portal vein occlusion (Pringle maneuver) were significantly associated with drain placement (p < 0.05). In the matched cohort (n = 190 in each arm), patients with surgical drains experienced higher rates of major morbidity (30% vs 12%), organ/space SSI (16% vs 6%), postoperative drain/aspiration procedures (9% vs 3%), and sepsis/septic shock (12% vs 4%) (all p < 0.05). Patients with severely prolonged drain removal, defined as after postoperative day 13 (POD13), had higher risk of postoperative morbidity compared to those with earlier drain removal (p < 0.01). 30-day mortality rate was not significantly different between the two groups. CONCLUSION: Primary surgical drains were placed in a substantial percentage of patients undergoing combined resection for sCRLM. This case-matched analysis suggested that surgical drains are associated with an increase in postoperative morbidity. Postoperative drain maintenance past 13 days is associated with worse outcomes compared to earlier removal.

Quadriceps Weakness After Single-Shot Adductor Canal Block: A Multivariate Analysis of 1,083 Primary Total Knee Arthroplasties.

BACKGROUND: Adductor canal blocks (ACBs) are commonly employed in multimodal pain control for total knee arthroplasty (TKA) and minimize motor blockade compared with femoral nerve blocks. Quadriceps weakness may be associated with ACBs. The purpose of this study was to quantify the prevalence of clinically relevant quadriceps weakness after a single-shot ACB and to identify the factors that are associated with its diagnosis. METHODS: The study group consisted of 1,083 retrospectively reviewed consecutive TKAs that were performed with ACBs at an academic hip and knee center. Quadriceps weakness was quantified with a standardized rating system during the initial physical therapy evaluation, and 23 potential covariates were analyzed. RESULTS: The prevalence of quadriceps weakness was 9%. Increasing the dose of the ACB anesthetic per unit of body mass index (BMI) increased the probability of quadriceps weakness by 5.0 times (95% confidence interval [CI], 1.9 to 13.3; p = 0.001). The highest probability of quadriceps weakness (52.9%) was associated with women who received the highest anesthetic dose per unit of BMI and an epinephrine extender but no corticosteroid extender. CONCLUSIONS: The optimal volume of local anesthetic in ACBs to maintain pain control while minimizing quadriceps weakness has not yet been defined. Our observation that quadriceps weakness was associated with increasing doses of ACB anesthetic per unit of BMI suggests that more than traditional structural canal-fill parameters (i.e., filling the distal aspect of the adductor canal without spreading to the femoral triangle) should be considered when choosing injectates and injectate volumes for ACBs. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Propensity-Matched Outcomes of Transcarotid Artery Revascularization Versus Carotid Endarterectomy.

BACKGROUND: Transcarotid artery revascularization (TCAR) with cerebral flow reversal is an emerging treatment option for carotid artery stenosis in patients with high risk for traditional endarterectomy. The purpose of this study was to compare real-world, procedure-related outcomes in similarly comorbid patients undergoing TCAR or carotid endarterectomy (CEA). METHODS: A retrospective review of all patients receiving either TCAR or CEA outside of clinical trial regulations at our institution was performed. Participants were propensity-matched by age, gender, body mass index, smoking status, presence of restenosis, history of neck radiation, presence of contralateral carotid occlusion, history of previous neck dissection, and symptom status. Bivariate analysis was followed by a penalized Firth logistic regression to compare treatments. RESULTS: Between January 2011 and July 2018, 342 CEAs and 109 TCARs were captured for analysis. After matching, 87 distinct treatment pairs were created without evidence of variation in any of the prespecified variables. On multivariate analysis using maximum and penalized likelihood ratios, we found that TCAR was associated with an increased incidence of intraoperative hypertension (adjusted coefficient, 1.41; 95% confidence interval [0.53, 2.29], P < 0.01). TCAR was also associated with decreased reverse flow/clamp time (mins; -36.80; [-45.47, -27.93], P < 0.01) and estimated blood loss (mLs; -63.66; [-85.91, -41.42], P < 0.01). In the perioperative period, there were no differences between TCAR and CEA with respect to myocardial infarction (-0.04; [-3.68, 3.60], P = 0.98), stroke (-0.74; [-2.68, 1.19], P = 0.45), and all-cause mortality (1.09; [-1.76, 3.94], P = 0.11). Similarly, a composite incidence of stroke/death was the same between cohorts (2.42; [-0.57, 5.41], P = 0.11). CONCLUSIONS: This propensity-matched analysis of carotid artery revascularization modalities suggests that TCAR is equivalent to CEA in the perioperative period while incurring shorter operative time and less blood loss.

The morbidity of C. difficile in necrotizing pancreatitis.

INTRODUCTION: Necrotizing pancreatitis (NP) patients commonly require antibiotic treatment during the several month-long disease course. We hypothesized that Clostridium difficile infection (CDI) is common in NP and significantly impacts outcomes. MATERIALS AND METHODS: Retrospective review of 704 NP patients treated at a single-institution (2005-2018). RESULTS: 10% (67/704) of patients developed CDI a mean 78 days after NP onset. Patients developing CDI experienced increased total hospital days (CDI, 104; No CDI, 42; P < 0.001), readmission rates (CDI, 85%; No CDI, 64%; P = 0.006), and duration of NP (CDI, 248 days; No CDI, 183; P = 0.001). Risk factors for CDI included antibiotic use (OR, 96.2; 95% CI, 5.9-1556.2; P = 0.001) and any organ failure (OR, 2.0; 95% CI, 1.2-3.3, P = 0.008). Mortality was not affected by CDI (CDI, 10%; No CDI, 9%; P = 0.7). CONCLUSION: Clostridium difficile infection is common in necrotizing pancreatitis and negatively impacts morbidity and disease recovery.

Combined transbrachial and transfemoral strategy to deploy an iliac branch endoprosthesis in the setting of a pre-existing endovascular aortic aneurysm repair.

This article describes brachial access to position a long sheath in the abdominal aorta in conjunction with a large caliber sheath via the femoral artery ipsilateral to the target site to deliver a 0.018 bodyfloss wire. This bodyfloss wire is inserted into the precannulation port of the iliac branch endoprosthesis (W. L. Gore and Associates, Flagstaff, Ariz), which is then advanced from the groin. Once the bifurcated device is deployed, hypogastric access and stenting is achieved from the upper extremity. This technique is an alternative to safely extend the distal seal while preserving the hypogastric artery and has the advantage of limited iliac bifurcation manipulation.

The Effect of Tourniquet Use and Sterile Carbon Dioxide Gas Bone Preparation on Cement Penetration in Primary Total Knee Arthroplasty.

BACKGROUND: Tourniquetless total knee arthroplasty (TKA) is experiencing resurgence in popularity due to potential pain control benefits. Furthermore, optimal cement technique and implant fixation remain paramount to long-term cemented TKA success, as aseptic loosening continues to be a leading cause of revision. The purpose of this study is to determine how tourniquet use and/or novel bone preparation using sterile, compressed carbon dioxide (CO2) gas affected cement penetration in TKA. METHODS: A retrospective review was performed on 303 consecutive primary TKAs with the same implant in 3 groups: (1) a tourniquet without sterile CO2 compressed gas used for bone preparation, (2) no tourniquet with CO2 gas, and (3) tourniquet use and CO2 gas bone preparation. Cement penetration was measured on radiographs by two independent, blinded raters across 7 zones defined by the Knee Society Radiographic Evaluation System. RESULTS: The 3 groups did not differ on age, body mass index, or gender (P ≥ .1). Cement penetration was greater in 6 of 7 zones with significantly greater cement penetration in 3 zones (tibial anteroposterior zone 2, femoral lateral zones 3A and 3P) in groups that utilized CO2 gas bone preparation compared to the tourniquet only group (P ≤ .039). CONCLUSION: Bone prepared with CO2 gas showed significantly more cement penetration in 3 zones with greater cancellous bone. The results suggest that use of CO2 gas bone preparation may achieve greater cement penetration than using a tourniquet with lavage only.