Immune checkpoint inhibitors in hepatocellular carcinoma: A review of current clinical trials.

Hepatocellular carcinoma (HCC) is the most common primary liver cancer with a poor prognosis due to advanced disease presentation or recurrence despite curative-intent resection. Since the approval of sorafenib in 2007, few systemic therapies offered a significant improvement in treatment outcomes. Over the last 3 years, however, rapid advancements in the field of immunotherapy have led to approval of checkpoint inhibitors in 2020 for use in advanced HCC.

The Connell Stitch: A Two-Generation Contribution to Gastrointestinal Surgery.

The history of the Connell Stitch begins at the Milwaukee County Hospital in 1887 and continues across two generations of surgeons, Dr. M.E.

Automated machine learning (AutoML) can predict 90-day mortality after gastrectomy for cancer.

Early postoperative mortality risk prediction is crucial for clinical management of gastric cancer. This study aims to predict 90-day mortality in gastric cancer patients undergoing gastrectomy using automated machine learning (AutoML), optimize models for preoperative prediction, and identify factors influential in prediction. National Cancer Database was used to identify stage I-III gastric cancer patients undergoing gastrectomy between 2004 and 2016.

Facility type is associated with improved perioperative and oncologic outcomes after minimally invasive surgery for pancreatic cancer.

Background: This study sought to evaluate outcome differences by facility type in patients who underwent minimally invasive surgery (MIS) for pancreatic ductal adenocarcinoma (PDAC).

Methods: The National Cancer Database was used to identify patients with clinical stage I-III PDAC who underwent MIS from 2010 to 2019 in academic or community facilities.

Results: Of 6806 patients who fulfilled inclusion criteria; 1788 (26.

Patterns of Unnecessary Insurer Prior Authorization Denials in a Complex Surgical Oncology Practice.

Introduction: Insurance prior authorization (PA) is a determination of need, required by a health insurer for an ordered test/procedure. If the test/procedure is denied, a peer-to-peer (P2P) discussion between ordering provider and payer is used to appeal the decision. The objective of this study was to measure the number and patterns of unnecessary PA denials.

Outcomes of plastic surgical reconstruction in extremity and truncal soft tissue sarcoma: Results from the US Sarcoma Collaborative.

Background: This study aimed to define how utilization of plastic surgical reconstruction (PSR) affects perioperative outcomes, locoregional recurrence-free survival (LRRFS), and overall survival (OS) after radical resection of extremity and truncal soft tissue sarcoma (ETSTS). The secondary aim was to determine factors associated with PSR.

Methods: Patients who underwent resection of ETSTS between 2000 and 2016 were identified from a multi-institutional database.

A Systematic Review of Conversion to Resectability in Unresectable Metastatic Colorectal Cancer Chemotherapy Trials.

Objectives: Metastasectomy in patients with metastatic colorectal cancer (mCRC) confers a significant survival benefit. We hypothesized that conversion to resectability (C2R) correlates with superior overall survival (OS) in patients with unresectable mCRC.

Methods: A prospectively registered systematic review (PROSPERO CRD42015024104) of randomized clinical trials published after 2003 was conducted.

Tau Aggregation Inducer Molecules Influence the Effects of Mutations on Aggregation Dynamics.

Alzheimer's disease (AD) and Alzheimer's disease-related dementias (ADRDs) affect 6 million Americans, and they are projected to have an estimated health care cost of $355 billion for 2021. A histopathological hallmark of AD and many ADRDs is the aberrant intracellular accumulation of the microtubule-associated protein tau. These neurodegenerative disorders that contain tau aggregates are collectively known as tauopathies, and recent structural studies have shown that different tauopathies are characterized by different "strains" of tau filaments.

Palliative Cytoreductive Surgery With or Without Hyperthermic Intraperitoneal Chemotherapy for Peritoneal Carcinomatosis: Is It Safe and Effective?

Introduction: Palliation is a controversial indication for cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). Patients with peritoneal carcinomatosis (PC) are living longer, and the roles of palliative CRS and HIPEC are increasingly challenged. The purpose of this study is to evaluate indications, morbidity, and symptom improvement from CRS/HIPEC in advanced PC.

Comparison of Hepatic Arterial Infusion Pump Chemotherapy vs Resection for Patients With Multifocal Intrahepatic Cholangiocarcinoma.

Importance: Intrahepatic cholangiocarcinoma (iCCA) is often multifocal (ie, satellites or intrahepatic metastases) at presentation.

Objective: To compare the overall survival (OS) of patients with multifocal iCCA after hepatic arterial infusion pump (HAIP) floxuridine chemotherapy vs resection.

Design, Setting, And Participants: In this cohort study, patients with histologically confirmed, multifocal iCCA were eligible.

First clinical-grade porcine kidney xenotransplant using a human decedent model.

A radical solution is needed for the organ supply crisis, and the domestic pig is a promising organ source. In preparation for a clinical trial of xenotransplantation, we developed an in vivo pre-clinical human model to test safety and feasibility tenets established in animal models. After performance of a novel, prospective compatible crossmatch, we performed bilateral native nephrectomies in a human brain-dead decedent and subsequently transplanted two kidneys from a pig genetically engineered for human xenotransplantation.

Conversion to resection post radioembolization in patients with HCC: recommendations from a multidisciplinary working group.

Background: Transarterial radioembolization (TARE) with yttrium-90 (Y) glass microspheres is an efficacious option for converting appropriately selected patients with borderline-resectable hepatocellular carcinoma (HCC) to surgical candidacy.

Methods: In 2018 and 2019, a diverse multidisciplinary group of surgical and interventional experts with experience using Y for downstaging and bridging to liver transplant convened to review peer-reviewed literature and personal experience in the use of Y to convert borderline resectable liver cancer patients to surgical candidacy. The working group included surgical oncologists specializing in liver cancer, liver transplant surgeons with experience in complex hepatobiliary surgery, and interventional radiologists with experience using Y.

Scalable Comparative Visualization of Ensembles of Call Graphs.

Optimizing the performance of large-scale parallel codes is critical for efficient utilization of computing resources. Code developers often explore various execution parameters, such as hardware configurations, system software choices, and application parameters, and are interested in detecting and understanding bottlenecks in different executions. They often collect hierarchical performance profiles represented as call graphs, which combine performance metrics with their execution contexts.

The BET Inhibitor JQ1 Augments the Antitumor Efficacy of Gemcitabine in Preclinical Models of Pancreatic Cancer.

Gemcitabine is used to treat pancreatic cancer (PC), but is not curative. We sought to determine whether gemcitabine + a BET bromodomain inhibitor was superior to gemcitabine, and identify proteins that may contribute to the efficacy of this combination. This study was based on observations that cell cycle dysregulation and DNA damage augment the efficacy of gemcitabine.

Fungally Derived Isoquinoline Demonstrates Inducer-Specific Tau Aggregation Inhibition.

The microtubule-associated protein tau promotes the stabilization of the axonal cytoskeleton in neurons. In several neurodegenerative diseases, such as Alzheimer's disease, tau has been found to dissociate from microtubules, leading to the formation of pathological aggregates that display an amyloid fibril-like structure. Recent structural studies have shown that the tau filaments isolated from different neurodegenerative disorders have structurally distinct fibril cores that are specific to the disease.

The Utility of Preoperative Tumor Markers in Peritoneal Carcinomatosis from Primary Appendiceal Adenocarcinoma: an Analysis from the US HIPEC Collaborative.

Background: Prognostication based on preoperative clinical factors is lacking in patients undergoing cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC). This study aims to determine the value of preoperative tumor markers as predictors of progression-free survival (PFS) and overall survival (OS) for patients with peritoneal carcinomatosis from a primary mucinous adenocarcinoma of the appendix (MACA).

Methods: We queried the United States HIPEC Collaborative, a database of patients with peritoneal carcinomatosis treated with CRS/HIPEC at twelve institutions between 2000 and 2017, identifying 409 patients with MACA.

Two-Stage Hepatectomy for Bilateral Colorectal Liver Metastases: A Multi-institutional Analysis.

Background: Two-stage hepatectomy (TSH) is an important tool in the management of bilateral colorectal liver metastases (CRLM). This study sought to examine the presentation, management, and outcomes of patients completing TSH in major hepatobiliary centers in the United States (US).

Methods: A retrospective review from five liver centers in the US identified patients who completed a TSH procedure for bilateral CRLM.

Impact of resection margin on outcomes in high-grade soft tissue sarcomas of the extremity-A USSC analysis.

Background: The optimal margin of resection for high-grade extremity sarcomas and its impact on survival has long been questioned in the setting of adjuvant radiotherapy. The objective of this study was to investigate the impact of resection status on recurrence and survival.

Methods: All patients with primary, nonmetastatic, high-grade extremity sarcomas that underwent surgical resection from January 2000 to April 2016 in the U.

Development of gemcitabine-resistant patient-derived xenograft models of pancreatic ductal adenocarcinoma.

Aim: Gemcitabine is a frontline agent for locally-advanced and metastatic pancreatic ductal adenocarcinoma (PDAC), but neither gemcitabine alone nor in combination produces durable remissions of this tumor type. We developed three PDAC patient-derived xenograft (PDX) models with gemcitabine resistance (gemR) acquired , with which to identify mechanisms of resistance relevant to drug exposure and to evaluate novel therapies.

Methods: Mice bearing independently-derived PDXs received 100 mg/kg gemcitabine once or twice weekly.

A closer look at the natural history and recurrence patterns of high-grade truncal/extremity leiomyosarcomas: A multi-institutional analysis from the US Sarcoma Collaborative.

Background/objective: Natural history and outcomes for truncal/extremity (TE) soft tissue sarcoma (STS) is derived primarily from studies investigating all histiotypes as one homogenous cohort. We aimed to define the recurrence rate (RR), recurrence patterns, and response to radiation of TE leiomyosarcomas (LMS).

Methods: Patients from the US Sarcoma Collaborative database with primary, high-grade TE STS were identified.

Mitochondrial DNA Manipulations Affect Tau Oligomerization.

Background: Mitochondrial dysfunction and tau aggregation occur in Alzheimer's disease (AD), and exposing cells or rodents to mitochondrial toxins alters their tau.

Objective: To further explore how mitochondria influence tau, we measured tau oligomer levels in human neuronal SH-SY5Y cells with different mitochondrial DNA (mtDNA) manipulations.

Methods: Specifically, we analyzed cells undergoing ethidium bromide-induced acute mtDNA depletion, ρ0 cells with chronic mtDNA depletion, and cytoplasmic hybrid (cybrid) cell lines containing mtDNA from AD subjects.

High neutrophil-lymphocyte ratio is not independently associated with worse survival or recurrence in patients with extremity soft tissue sarcoma.

Background: Soft tissue sarcomas are a heterogenous group of neoplasms without well-validated biomarkers. Cancer-related inflammation is a known driver of tumor growth and progression. Recent studies have implicated a high circulating neutrophil-lymphocyte ratio as a surrogate marker for the inflammatory tumor microenvironment and a poor prognosticator in multiple solid tumors, including colorectal and pancreatic cancers.

Comparison of overall survival in gallbladder carcinoma at academic versus community cancer centers: An analysis of the National Cancer Data Base.

Background And Objectives: Gallbladder carcinoma (GBC) has a poor prognosis. Studies demonstrated that teaching facilities may provide a lower risk of mortality in patients undergoing pancreatic and colon resection vs nonteaching facilities. We hypothesized that survival rates are higher in academic cancer centers (ACCs) vs community cancer centers (CCCs).

Outcomes of palliative-intent surgery in retroperitoneal sarcoma-Results from the US Sarcoma Collaborative.

Background And Objectives: Outcomes of palliative-intent surgery in retroperitoneal sarcomas (RPS) are not well understood. This study aims to define indications for and outcomes after palliative-intent RPS resection.

Methods: Using a retrospective 8-institution database, patients undergoing resection of primary/recurrent RPS with palliative intent were identified.