Compromised macrophages contribute to progression of MASH to hepatocellular carcinoma in FGF21KO mice.

Metabolic dysfunction-associated steatohepatitis is well accepted as a potential precursor of hepatocellular carcinoma. Previously, we reported that fibroblast growth factor 21 (FGF21) revealed a novel anti-inflammatory activity via inhibiting the TLR4-IL-17A signaling, which could be a potential anticarcinogenetic mechanism to prevent to MASH-HCC transition. Here, we set out to determine whether FGF21 has a major impact on Kupffer cells' (KCs) ability during MASH-HCC transition.

Developing sarcopenia during neoadjuvant therapy is associated with worse survival in esophageal adenocarcinoma patients.

Background: Sarcopenia in cancer patients has been associated with mixed postoperative outcomes. The aim of this study was to evaluate whether the development of sarcopenia during the neoadjuvant period is predictive of postoperative mortality in esophageal adenocarcinoma patients.

Methods: We queried a prospective database to retrieve the sarcopenic status of patients with esophageal adenocarcinoma who underwent cross-sectional imaging of the third lumbar vertebra at diagnosis and within 2 months of undergoing an esophagogastrectomy between 2014 and 2022.

Who posted #MeToo, why, and what happened: A mixed methods examination.

Objectives: The #MeToo social media campaign raised awareness about sexual harassment. The purpose of the current study was to address three unexplored research questions. First, what factors influenced whether a person posted #MeToo? Second, how did posting (or not) influence participants' wellbeing? Finally, what motivated participants' posting (or not) #MeToo?

Method: This mixed-methods study explores how #MeToo was experienced by full-time employees ( = 395) who could have posted #MeToo (i.

S1PR1/S1PR3-YAP signaling and S1P-ALOX15 signaling contribute to an aggressive behavior in obesity-lymphoma.

Background: Excess body weight has been found to associate with an increased risk of lymphomas and some metabolic pathways are currently recognized in lymphomagenesis. Bioactive lipid metabolites such as sphingosine-1-phosphate (S1P) have been proposed to play an important role linking obesity and lymphomas. However, the underlying mechanism(s) of S1P signaling in obesity-lymphomagenesis have not been well addressed.

Epigenetic modulation enhances immunotherapy for pancreatic ductal adenocarcinoma.

Objectives: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease with a poor prognosis. PDAC has poor response to immunotherapy because of its unique tumour microenvironment (TME). In an attempt to stimulate immunologically silent pancreatic cancer, we investigated the role of epigenetic therapy in modulating the TME to improve immunogenicity.

Laparoscopic microwave ablation versus percutaneous microwave ablation of hepatic malignancies: Efficacy and recurrence-free survival outcomes in patients.

Background: Hepatic thermal ablation has been found to be effective and equivalent to resection in certain liver histologies. Of the 16,000 annual liver ablations performed in the United States, only 13% (2,080 ablations) are performed laparoscopically. The laparoscopic technique remains underused even with the benefits of improved staging and better access to tumors.

Intraoperative Pancreatic Neck Margin Assessment During Pancreaticoduodenectomy for Pancreatic Adenocarcinoma in the Era of Neoadjuvant Therapy: A Multi-institutional Analysis from the Central Pancreatic Consortium.

Background: Data regarding the survival impact of converting frozen-section (FS):R1 pancreatic neck margins to permanent section (PS):R0 by additional resection (i.e., converted-R0) during upfront pancreaticoduodenectomy for pancreatic ductal adenocarcinoma (PDAC) are conflicting.

Aberrant FGFR4 signaling worsens nonalcoholic steatohepatitis in FGF21KO mice.

Nonalcoholic steatohepatitis (NASH) is the most severe form of non-alcoholic fatty liver disease (NAFLD) and a potential precursor of hepatocellular carcinoma (HCC). In our previous studies, we found that endocrine fibroblast growth factor 21 (FGF21) played a key role in preventing the development of NASH, however, the FGF15/19 mediated-FGFR4 signaling worsened NASH and even contributed to the NASH-HCC transition. The aim of this study is to determine whether FGF15/FGFR4 signaling could alleviate or aggravate NASH in the FGF21KO mice.

Irreversible electroporation enhances immunotherapeutic effect in the off-target tumor in a murine model of orthotopic HCC.

Irreversible electroporation (IRE) has been postulated to have an off-target effect on lesions not in the tumor-ablative field, possibly through heightened immunologic response. In this study, we evaluated whether combination IRE and immunotherapy would lead to increased tumor necrosis and T cell recruitment to both the treated tumors and tumors outside the local ablative field. An cell-IRE model was established to evaluate the ability of T lymphocytes (EL4 cell and HH cells) migration in response to Hepatocellular carcinoma (HCC) cells (Hepa1-6 and HepG2) with IRE treatment.

Lack of FGF21 promotes NASH-HCC transition hepatocyte-TLR4-IL-17A signaling.

Hepatocellular carcinoma (HCC) has been increasingly recognized in nonalcoholic steatohepatitis (NASH) patients. Fibroblast growth factor 21 (FGF21) is reported to prevent NASH and delay HCC development. In this study, the effects of FGF21 on NASH progression and NASH-HCC transition and the potential mechanism(s) were investigated.

Enhanced recovery after surgery is safe for cytoreductive surgery with hyperthermic intraperitoneal chemotherapy.

Introduction: Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) is an effective, aggressive approach to treating intraperitoneal carcinomatosis. This study aimed to test the efficacy/safety of an enhanced recovery (ERAS) program after CRS-HIPEC surgery.

Methods: Review of an IRB-approved prospectively maintained HIPEC database from 2003 to 2019.

Transarterial Chemoembolization vs Radioembolization for Neuroendocrine Liver Metastases: A Multi-Institutional Analysis.

Background: Liver-directed hepatic arterial therapies are associated with improved survival and effective symptom control for patients with unresectable neuroendocrine liver metastases (NELM). Whether transarterial chemoembolization (TACE) or transarterial radioembolization (TARE) with yttrium-90 (y-90) are associated with improved short- or long-term outcomes is unknown.

Study Design: A retrospective review was performed of all patients with NELM undergoing transarterial therapies, from 2000 to 2018, at 2 academic medical centers.

A novel theranostic gold nanorods- and Adriamycin-loaded micelle for EpCAM targeting, laser ablation, and photoacoustic imaging of cancer stem cells in hepatocellular carcinoma.

Introduction And Purpose: Cancer stem cells (CSCs) present a higher capacity to evade being killed by cancer agents and developing chemoresistance, thus leading to failure of conventional anticancer therapeutics. Nanomaterials specifically designed for targeting and treating not only tumor cells, but also CSCs, may encompass therapeutic and diagnostic tools, thus successfully eradicating the tumor.

Materials And Methods: Polymeric micelles simultaneously loaded with gold nanorods (GNRs) and Adriamycin were prepared and used as a novel therapeutic and diagnostic weapon.

Should Sentinel Lymph Node Biopsy Be Performed for All T1b Melanomas in the New 8 Edition American Joint Committee on Cancer Staging System?

Background: In the 8 edition of the American Joint Committee on Cancer melanoma staging system, the T1b category has been redefined based solely on thickness and ulceration. National Comprehensive Cancer Network guidelines recommend consideration of sentinel lymph node biopsy (SLNB) for all patients with T1b melanomas (0.8 to 1.

Cyst location and presence of high grade dysplasia or invasive cancer in intraductal papillary mucinous neoplasms of the pancreas: a seven institution study from the central pancreas consortium.

Background: Traditionally, intraductal papillary mucinous neoplasms (IPMNs) of the pancreas with "high risk stigmata" (HRS) or "worrisome features" (WF) are referred for resection. We aim to assess if IPMN location is predictive of harboring either high grade dysplasia (HGD) or invasive cancer (IC).

Methods: Patients undergoing resection for IPMN from seven institutions between 2000 and 2015 (n = 275) were analyzed.

Serological biomarkers associate ultrasound characteristics of steatohepatitis in mice with liver cancer.

Background: Non-alcoholic fatty liver disease (NAFLD) covers a spectrum of lesions ranging from steatosis to a complex pattern, nonalcoholic steatohepatitis (NASH). Ultrasonography provides important information on hepatic architecture for steatosis. NASH patients have an increased risk of hepatocellular carcinoma (HCC).

Up-regulation of FGF15/19 signaling promotes hepatocellular carcinoma in the background of fatty liver.

Background: Upregulated fibroblast growth factor 19 (FGF19) expression in human hepatocellular carcinoma (HCC) specimens is associated with tumor progression and poor prognosis. Nonalcoholic steatohepatitis (NASH) patients are at high risk for malignant transformation into HCC.

Methods: A steatohepatitis-HCC model was established in male C57L/J mice treated with N-nitrosodiethylamine (DEN) and high-fat diet (HFD).

Multigene Signature Panels and Breast Cancer Therapy: Patterns of Use and Impact on Clinical Decision Making.

Background: A growing body of evidence supports the use of multigene signature panels (MSPs) in predicting recurrence risk in patients with invasive breast cancer. This study aimed to evaluate trends in MSP use over time and the effect of MSPs on administration of postoperative chemotherapy.

Study Design: The National Cancer Database was queried for all women with invasive breast cancer who underwent resection between 2011 and 2014 and had information about performance of an MSP, hormone receptor status, and receipt of chemotherapy.

Induction Chemotherapy Followed by Resection or Irreversible Electroporation in Locally Advanced Pancreatic Cancer (IMPALA): A Prospective Cohort Study.

Background: Following induction chemotherapy, both resection or irreversible electroporation (IRE) may further improve survival in patients with locally advanced pancreatic cancer (LAPC). However, prospective studies combining these strategies are currently lacking, and available studies only report on subgroups that completed treatment. This study aimed to determine the applicability and outcomes of resection and IRE in patients with nonprogressive LAPC after induction chemotherapy.

Are the Current Guidelines for the Surgical Management of Intraductal Papillary Mucinous Neoplasms of the Pancreas Adequate? A Multi-Institutional Study.

Background: Controversy persists regarding the management of patients with intraductal papillary mucinous neoplasms (IPMN). International consensus guidelines stratify patients into high-risk, worrisome, and low risk categories.

Study Design: The medical records of 7 institutions were reviewed for patients who underwent surgical management of IPMN between 2000 and 2015.

Distal Cholangiocarcinoma and Pancreas Adenocarcinoma: Are They Really the Same Disease? A 13-Institution Study from the US Extrahepatic Biliary Malignancy Consortium and the Central Pancreas Consortium.

Background: Distal cholangiocarcinoma (DC) and pancreatic ductal adenocarcinoma (PDAC) are often managed as 1 entity, yet direct comparisons are lacking. Our aim was to use 2 large multi-institutional databases to assess treatment, pathologic, and survival differences between these diseases.

Study Design: This study included patients with DC and PDAC who underwent curative-intent pancreaticoduodenectomy from 2000 to 2015 at 13 institutions comprising the US Extrahepatic Biliary Malignancy and Central Pancreas Consortiums.

Intrapancreatic accessory spleen (IPAS): A single-institution experience and review of the literature.

Introduction: Accessory spleens located within the pancreatic parenchyma (intrapancreatic accessory spleen, IPAS) pose a unique clinical challenge. In many cases, despite imaging and other diagnostic studies, malignancy cannot be excluded and patients are subjected to pancreatic resection. We review our experience with the presentation, diagnosis, and treatment of patients with IPAS to provide insight into improving pre-operative evaluation of these patients METHODS: A retrospective chart review identified seven patients who underwent surgical resection of an intrapancreatic spleen at University of Louisville Hospital between 2004 and 2015.

Management of Locally Advanced Pancreatic Cancer.

The diagnosis for locally advanced pancreatic cancer is based on high-quality cross-sectional imaging, which shows tumor invasion into the celiac/superior mesenteric arteries and/or superior mesenteric/portal venous system that is not reconstructable. The optimal management of these patients is evolving quickly with the advent of newer chemotherapeutics, radiation, and nonthermal ablation modalities. This article presents the current status of initial chemotherapy, surgical therapy, ablative therapy, and radiation therapy for patients with nonmetastatic locally advanced unresectable pancreatic cancer.

A Novel Pathology-Based Preoperative Risk Score to Predict Locoregional Residual and Distant Disease and Survival for Incidental Gallbladder Cancer: A 10-Institution Study from the U.S. Extrahepatic Biliary Malignancy Consortium.

Background: This study was designed to develop a more robust predictive model, beyond T-stage alone, for incidental gallbladder cancer (IGBC) for discovering locoregional residual (LRD) and distant disease (DD) at reoperation, and estimating overall survival (OS). T-stage alone is currently used to guide treatment for incidental gallbladder cancer. Residual disease at re-resection is the most important factor in predicting outcomes.