Atezolizumab for Advanced Alveolar Soft Part Sarcoma.

Background: Alveolar soft part sarcoma (ASPS) is a rare soft-tissue sarcoma with a poor prognosis and no established therapy. Recently, encouraging responses to immune checkpoint inhibitors have been reported.

Methods: We conducted an investigator-initiated, multicenter, single-group, phase 2 study of the anti-programmed death ligand 1 (PD-L1) agent atezolizumab in adult and pediatric patients with advanced ASPS.

Challenges and next steps in the advancement of immunotherapy: summary of the 2018 and 2020 National Cancer Institute workshops on cell-based immunotherapy for solid tumors.

Cell-based immunotherapies have had remarkable success in the clinic, specifically in the treatment of hematologic malignancies. However, these strategies have had limited efficacy in patients with solid tumors. To better understand the challenges involved, the National Cancer Institute (NCI) convened an initial workshop with immuno-oncology thought leaders in December 2018 and a follow-up workshop in December 2020.

A phase I pharmacokinetic study of belinostat in patients with advanced cancers and varying degrees of liver dysfunction.

Aims: The histone deacetylase inhibitor belinostat has activity in various cancers. Because belinostat is metabolized by the liver, reduced hepatic clearance could lead to excessive drug accumulation and increased toxicity. Safety data in patients with liver dysfunction are needed for this drug to reach its full potential in the clinic.

The NCI Transcriptional Pharmacodynamics Workbench: A Tool to Examine Dynamic Expression Profiling of Therapeutic Response in the NCI-60 Cell Line Panel.

: The intracellular effects and overall efficacies of anticancer therapies can vary significantly by tumor type. To identify patterns of drug-induced gene modulation that occur in different cancer cell types, we measured gene-expression changes across the NCI-60 cell line panel after exposure to 15 anticancer agents. The results were integrated into a combined database and set of interactive analysis tools, designated the NCI Transcriptional Pharmacodynamics Workbench (NCI TPW), that allows exploration of gene-expression modulation by molecular pathway, drug target, and association with drug sensitivity.

Augmented Th17 Differentiation Leads to Cutaneous and Synovio-Entheseal Inflammation in a Novel Model of Psoriatic Arthritis.

Objective: To introduce a novel preclinical animal model of psoriatic arthritis (PsA) in R26Stat3C CD4Cre mice, and to investigate the role of Th17 cytokines in the disease pathogenesis.

Methods: We characterized a novel murine model of Th17-driven cutaneous and synovio-entheseal disease directed by T cell-specific expression of a hyperactive Stat3 allele. By crossing R26Stat3C CD4Cre mice onto an interleukin-22 (IL-22)-knockout background or treating the mice with a neutralizing antibody against IL-17, we interrogated how these Th17 cytokines could contribute to the pathogenesis of PsA.

Role of Dysregulated Cytokine Signaling and Bacterial Triggers in the Pathogenesis of Cutaneous T-Cell Lymphoma.

Cutaneous T-cell lymphoma is a heterogeneous group of lymphomas characterized by the accumulation of malignant T cells in the skin. The molecular and cellular etiology of this malignancy remains enigmatic, and what role antigenic stimulation plays in the initiation and/or progression of the disease remains to be elucidated. Deep sequencing of the tumor genome showed a highly heterogeneous landscape of genetic perturbations, and transcriptome analysis of transformed T cells further highlighted the heterogeneity of this disease.

Phosphorylated fraction of H2AX as a measurement for DNA damage in cancer cells and potential applications of a novel assay.

Phosphorylated H2AX (γ-H2AX) is a sensitive marker for DNA double-strand breaks (DSBs), but the variability of H2AX expression in different cell and tissue types makes it difficult to interpret the meaning of the γ-H2AX level. Furthermore, the assays commonly used for γ-H2AX detection utilize laborious and low-throughput microscopy-based methods. We describe here an ELISA assay that measures both phosphorylated H2AX and total H2AX absolute amounts to determine the percentage of γ-H2AX, providing a normalized value representative of the amount of DNA damage.

The combination of hypomethylating agents and histone deacetylase inhibitors produce marked synergy in preclinical models of T-cell lymphoma.

T-cell lymphomas (TCL) are aggressive lymphomas usually treated with CHOP (cyclophsophamide, doxorubicin, vincristine, prednisolone)-like regimens upfront. Recent data suggest that TCL are driven by epigenetic defects, potentially rendering them sensitive to epigenetic therapies. We explored the therapeutic merits of a combined epigenetic platform using histone deacetylase inhibitors (HDACIs) and DNA methyltransferase inhibitors (DNMT) in in vitro and in vivo models of TCL.

Development and characterization of a Mantle Cell Lymphoma Cell Bank in the American Type Culture Collection.

Mantle cell lymphoma (MCL) is a rare B-cell malignancy that carries a relatively poor prognosis compared to other forms of non-Hodgkin lymphoma. Standardized preclinical tools are desperately required to hasten the discovery and translation of promising new treatments for MCL. Via an initiative organized through the Mantle Cell Lymphoma Consortium and the Lymphoma Research Foundation, we gathered MCL cell lines from laboratories around the world to create a characterized MCL Cell Bank at the American Type Culture Collection (ATCC).

T cell-derived IL-17 mediates epithelial changes in the airway and drives pulmonary neutrophilia.

Th17 cells are a proinflammatory subset of effector T cells that have been implicated in the pathogenesis of asthma. Their production of the cytokine IL-17 is known to induce local recruitment of neutrophils, but the direct impact of IL-17 on the lung epithelium is poorly understood. In this study, we describe a novel mouse model of spontaneous IL-17-driven lung inflammation that exhibits many similarities to asthma in humans.

Mouse telomerase reverse transcriptase (mTert) expression marks slowly cycling intestinal stem cells.

The intestinal epithelium is maintained by a population of rapidly cycling (Lgr5(+)) intestinal stem cells (ISCs). It has been postulated, however, that slowly cycling ISCs must also be present in the intestine to protect the genome from accumulating deleterious mutations and to allow for a response to tissue injury. Here, we identify a subpopulation of slowly cycling ISCs marked by mouse telomerase reverse transcriptase (mTert) expression that can give rise to Lgr5(+) cells.

[Laparoscopic sleeve gastrectomy: technique and preliminary results].

According to the WHO about 300 million people in the world are affected by obesity with an increasing trend. The aim of the present study was to assess our preliminary results with sleeve gastrectomy. Over the period from June 2006 to March 2008, 25 laparoscopic sleeve gastrectomy were performed at our Department of Surgery for morbid obesity by the same surgeon.

Laparoscopic cholecystectomy without intraoperative cholangiography: audit of long-term results.

There is no uniform consensus on the utility of routine intraoperative cholangiography (IOC) during laparoscopic cholecystectomy (LC). In this paper, we present a 10-year retrospective audit of our cases of LC without IOC, performed by a search of readmission cases through our electronic database. Data regarding all patients subjected to LC at our unit in the period January 1996-December 2006 were obtained through our hospital database system.

[Laparoscopic surgical treatment of polycystic liver: a case report].

The preoperative diagnosis of polycystic liver is easily obtainable by ultrasound, while computed tomography is more sensitive for making the differential diagnosis versus other hepatic lesions. This report describes a case of polycystic liver with mass-related symptoms. A laparoscopic fenestration of the larger and superficial cysts was performed.

[Dysphagia after laparoscopic Nissen fundoplication].

The aim of the study was to consider all the factors associated with the development of postoperative dysphagia which, in its transitory form, can be present in as many as 40 to 70% of cases. From 1996 to 2007, 302 Nissen fundoplications were performed at our department of surgery. We divided this series into two groups, the first consisting of 149 cases (from March 1996 to March 2004) where short gastric vessels were not dissected (nl-VGB) and the second of 153 cases (from April 2004 to December 2007) where short gastric vessels were dissected (I-VGB).

[Radiofrequency Milligan-Morgan haemorrhoidectomy in the outpatient setting].

The demand for shorter admissions and quicker recoveries prompted us to adopt a new approach, favouring day surgery as the preferred organisational modality. Since 2004, 312 Milligan-Morgan haemorrhoidectomies have been performed at our department of surgery. The operations were performed at our proctological outpatient unit by means of LigasureTM with immediate discharge.

Avoiding complications after laparoscopic esophago-gastric banding: experience with 400 consecutive patients.

Background: Among bariatric operations, laparoscopic adjustable gastric banding (LAGB) has been the preferred one in Europe and Australia, and has become recently popular in the USA. Like every surgical procedure, however, it is not devoid of specific complications, like slippage, band erosion, outlet obstruction and port problems. Assuming that the absence of the pouch may avoid postoperative slippage, we introduced the technique of esophago-gastric placement, instead of the original gastric banding technique.

Conversion rate in laparoscopic cholecystectomy: evolution from 1993 and current state.

The definition of difficult laparoscopic cholecystectomy (LC) is inconsistent. The aim of this study was to analyze the factors that make LC difficult to perform and determine ways to avoid conversion, based on our series. All patients who underwent LC or open cholecystectomy (OC) between January 1993 and December 2001 in our division of general surgery were the subject matter of this study.

Long-term insulin independence following repeated islet transplantation in totally pancreatectomized diabetic pigs.

Clinical islet transplantation (Tx) in type I diabetic patients has been successful so far only in a minority of cases, probably because of multiple factors, partly immunologic and partly nonimmunologic in nature. Preclinical studies of islet Tx in large animals are still needed to clarify the reasons and find possible solutions. In this study, we tested the feasibility of noninvasive, repeated intrahepatic allo-Tx of porcine pancreatic islets obtained from multiple donors, in pigs rendered diabetic by total pancreatectomy (Pct).

Laparoscopic appendectomy for acute and recurrent appendicitis: retrospective analysis of a single-group 5-year experience.

Background And Purpose: Twenty years after the first report of laparoscopic appendectomy (LA), its role in the treatment of appendicitis is still under debate. We report herein a retrospective analysis of our cases of LA in the last 5 years, during which we adopted a policy of an almost uniform laparoscopic approach on a rather selected population composed mainly of women with acute or recurrent lower quadrant abdominal pain.

Patients And Methods: Laparoscopic appendectomy was performed on 33 male and 98 female patients.

[In vitro experimentation of a new model of radial flow bioreactor containing isolated hepatocytes].

Hepatocyte based artificial liver support systems are under investigation to support acute liver failure patients. The main purpose of such systems is to serve as a bridge to liver transplantation, or to promote spontaneous liver recovery. Limitation in mass-transfer capacity makes hollow-fiber bioreactors unsuited for long-term functioning of hybrid devices.

[Acute and fulminant liver failure: experimental models].

Fulminant hepatic failure (FHF) is a complex clinical syndrome, with an invariably high mortality rate, that follows many possible and different infectious, pharmacologic and surgical liver injuries. The appearance of the syndrome is similar whatever the etiology, but the mechanisms which lead to the development of FHF are greatly varied. In order to understand the possible pathways which drive to FHF, experimental animal models have been used for a long time.

[Fulminant liver failure: etiopathogenesis and therapy].

Fulminant hepatic failure (FHF) is a clinical syndrome characterized by the development of encephalopathy within eight weeks from the onset of the first symptoms, in the absence of previous hepatic disease. It is an uncommon but not rare disease, often fatal but potentially reversible. This article looks at the diverse aetiologies, clinical features, and current medical management, including orthotopic liver transplantation, and auxiliary orthotopic or eterotopic liver transplantation, that are the most recently adopted surgical procedures.