Management of Locally Recurrent Retroperitoneal Sarcoma in the Adult: An Updated Consensus Approach from the Transatlantic Australasian Retroperitoneal Sarcoma Working Group

Annals of Surgical Oncology - Surgery is the mainstay of treatment for retroperitoneal sarcoma (RPS), but local recurrence is common. Biologic behavior and recurrence patterns differ significantly...     

Parietal network underlying movement control: disturbances during subcortical electrostimulation

Our understanding of brain movement control has changed over the last two decades. Recent findings in the monkey and in humans have led to a parallel and interconnected network. Nevertheless, little is known about these networks. Here, we present two cases of patients with a parietal low-grade glioma. They underwent surgery under local anesthesia with cortical and subcortical mapping. For patient 1, subcortical electrostimulation immediately posterior to thalamocortical fibers induced movement disorders, with an inhibition of leg and arm movements medially and, more laterally, an acceleration of arm movement. For patient 2, electrostimulation of white matter immediately posterior to thalamocortical fibers induced an inhibition of both arm movement. It means that the detected fibers in the parietal lobe may be involved in the motor control modulation. They are distributed veil-like immediately posterior to thalamocortical pathways and could correspond to a fronto-parietal movement control subnetwork. These two cases highlight the major role of the subcortical connectivity in movement regulation, involving parietal lobe, thus the necessity to be identified and preserved during brain surgery.     

Results of a Surgeon-Directed Quality Improvement Project on Breast Cancer Surgery Outcomes in South-Central Ontario

Background

Gaps in breast cancer (BC) surgical care have been identified. We have completed a surgeon-directed, iterative project to improve the quality of BC surgery in South-Central Ontario.

Methods

Surgeons performing BC surgery in a single Ontario health region were invited to participate. Interventions included: audit and feedback (A&F) of surgeon-selected quality indicators (QIs), workshops, and tailoring interviews. Workshops and A&F occurred yearly from 2005–2012. QIs included: preoperative imaging; preoperative core biopsy; positive margin rates; specimen orientation labeling; intraoperative specimen radiography of nonpalpable lesions; T1/T2 mastectomy rates; reoperation for positive margins; sentinel lymph node biopsy (SLNB) rates, number of sentinel lymph nodes; and days to receive pathology report. Semistructured tailoring interviews were conducted to identify facilitators and barriers to improved quality. All results were disseminated to all surgeons performing breast surgery in the study region.

Results

Over 6 time periods, 1,828 BC charts were reviewed from 12 hospitals (8 community and 4 academic). Twenty-two to 40 participants attended each workshop. Sustained improvement in rates of positive margins, preoperative core biopsies, specimen orientation labeling, and SLNB were seen. Mastectomy rates and overall axillary staging rates did not change, whereas time to receive pathology report increased. The tailoring interviews concerning positive margins, SLNB, and reoperation for positive margins identified facilitators and barriers relevant to surgeons.

Conclusions

This surgeon-directed, regional project resulted in meaningful improvement in numerous QIs. There was consistent and sustained participation by surgeons, highlighting the importance of integrating the clinicians in a long-term, iterative quality improvement strategy in BC surgery.     

Presence of a mobilizable intracellular pool of hepatocyte growth factor in human polymorphonuclear neutrophils

Hepatocyte growth factor (HGF), a heparin-binding factor, is synthesized as a single-chain inactive precursor (pro-HGF), which is converted by proteolysis to an active heterodimer (mature HGF). HGF has pleiotropic activities and has been implicated in the regulation of mitogenesis, motogenesis, and morphogenesis of epithelial and endothelial cells. As polymorphonuclear neutrophils (PMNs) secrete numerous cytokines involved in the modulation of local inflammation, we investigated their ability to produce HGF. We found that HGF was stored in secretory vesicles and in gelatinase/specific granules. This intracellular stock was rapidly mobilized by degranulation when neutrophils were stimulated with phorbol myristate acetate or N-formylmethionyl-leucyl-phenylalanine. Cycloheximide did not affect the release of HGF. Moreover, HGF messenger RNA and protein expression was found in bone marrow myeloid cells, suggesting that HGF synthesis likely occurs during PMN maturation. In mature circulating PMNs, intracellular HGF was in the pro-HGF form, whereas the HGF secreted by degranulation was the mature form. Furthermore, PMNs pretreated with diisopropyl fluorophosphate only released the pro-HGF form, suggesting that PMN-derived serine protease(s) are involved in the proteolytic process. We also obtained evidence that secreted mature HGF binds PMN-derived glycosaminoglycans (probably heparan sulfate). These findings suggest that PMNs infiltrating damaged tissues may modulate local wound healing and repair through the production of HGF, a major mediator of tissue regeneration.     

Recombinant bovine growth hormone-induced reduction of atrial natriuretic peptide is associated with improved left ventricular contractility and reverse remodeling in cardiomyopathic UM-X7.1 hamsters with congestive heart failure.

OBJECTIVE: To assess the effect of short-term treatment with GH on left ventricular contractility and remodeling, after the development of heart failure in cardiomyopathic hamsters (CMH). DESIGN: Two groups of 200-day-old UM-X7.1 CMH received daily subcutaneous injections of recombinant bovine (rb) GH (1mg/kg/day) or 0.9% NaCl for 40 days. Golden Syrian hamsters (GSH) were used as controls. At 240-day-old, the hamsters were randomly subjected to (i) assessment of left ventricular systolic function in a Langendorff perfused mode followed by the determination of the passive diastolic pressure-volume relationship and morphometric measurements; (ii) assessment of left ventricular mRNA expression of genes belonging to the fetal gene program including atrial (ANP) and brain (BNP) natriuretic peptides and cardiac myosin heavy chain isoforms and of the circulating levels of the natriuretic peptides. RESULTS: Hearts from CMH were hypertrophied and dilated (p<0.05) compared to hearts from GSH, along with a approximately 10-fold increase in the circulating ANP and BNP levels. Left ventricular BNP and ANP mRNAs were elevated by 2- and 3-fold, respectively, compared to GSH. rbGH reduced both ANP mRNA and ANP circulating levels by 34% (p<0.01) but did not significantly modulate BNP levels. This effect was associated with a preserved systolic function and reverse remodeling as assessed by a leftward shift of the passive diastolic pressure-volume relationship indicating reduced ventricular dilatation. CONCLUSIONS: The data show that a short-term administration of GH in the terminal phase of the disease confers cardioprotection by attenuating systolic dysfunction and by inducing beneficial reverse remodeling.     

Patterns of intermediate filaments, VLA integrins and HLA antigens in a new human biliary epithelial cell line sensitive to interferon-γ

Background/Aims: Intra-hepatic bile ducts are the primary site of damage in several immunologically mediated liver diseaes. However, immunological processes underlying biliary epithelial cell recognition by T lymphocytes are poorly understood. Therefore, a convenient in vitro model that could mimic these immunologic disorders would be of great interest.Methods: A human cell line (HuGB) was established from a metastasis of gallbladder adenocarcinoma in the liver. Intermediate filament expression was analysed by immunostaining, and gamma-glutamyl transpeptidase and albumin secretion were measured. VLA integrin expression pattern, expression of HLA class I and II antigens and ICAM-1 protein were analysed by flow cytometry and their modulation by interferon-γ was quantitated using a QIFIKIT commercial kit.Results: Histological analysis showed high similarity between the initial gallbladder adenocarcinoma and the established cell line. Cytokeratins 8 and 19 and vimentin showed strong positive staining in the established cell line. Gamma-glutamyl transpeptidase was secreted by these cells while albumin expression was negative. HuGB cells also expressed VLA-α2, VLA-α3, VLA-α6, VLA-β1, but not VLA-α1, VLA-α4 and NCAM, a pattern of adhesion molecule expression compatible with the biliary epithelium. Also, similar to the biliary epithelium found in normal liver, HuGB cells expressed abundant HLA class I but few HLA class II antigens. We found that the expression of HLA antigens and ICAM-1 protein were increased during interferon-γ treatment of HuGB cell line.Conclusions: Both phenotypic and morphological characteristics of HuGB cells suggested their biliary origin. Sensitivity of HuGB cells to interferon-γ suggests that this new cell line could represent a suitable model to investigate the up-regulation of membrane antigens occurring in immune diseases involving biliary epithelial cells.