Johns Hopkins University School of Medicine

About: Johns Hopkins University School of Medicine is a healthcare organization based out in Baltimore, Maryland, United States. It is known for research contribution in the topics: Population & Medicine. The organization has 44277 authors who have published 79222 publications receiving 4788882 citations.

Pretreatment assessment of resectable and borderline resectable pancreatic cancer: expert consensus statement.

Abstract: Preoperative Staging and Defining Resectability From a surgical perspective, the first objective in the management of suspected or confirmed pancreatic cancer is to determine the potential for resection. Routine exploratory laparotomy for the purpose of operatively determining resectability has been diminished by modern 3-D radiographic imaging, along with effective and sustainable nonoperative methods of palliation. Careful correlation between preoperative CT findings and surgical results has better-defined CT criteria for resectability. The critical aspects that need be evaluated in a thorough radiographic assessment are the presence or absence of peritoneal or hepatic metastases; the potential involvement of the SMV and portal vein and the relationship of these vessels and their tributaries to the tumor; the relationship of the tumor to the SMA, celiac axis, hepatic artery, and gastroduodenal artery; and the presence of any aberrant vascular anatomy. Unequivocal radiographic findings contraindicating resection include distant metastases, major venous thrombosis of the portal vein or SMV extending for several centimeters, and circumferential encasement of the SMA, celiac axis or proximal hepatic artery. Recent revisions of the National Comprehensive Cancer Network (NCCN) guidelines were an attempt to distinguish locally advanced unresectable tumors from potentially resectable tumors.22 Ambiguity exists in these guidelines because of the lack of clarity in defining clearly resectable situations from “borderline resectable” tumors and because of the subjective criteria used to define “borderline” tumors relative to locally advanced, unresectable lesions. The NCCN guidelines do offer a definition of what should be considered a radiographically resectable tumor. Patients without distant metastases and no evidence of tumor extension to the SMV and portal vein and clear fat planes around the celiac axis, the hepatic artery, and SMA should be categorized as having localized and resectable cancers. More refined and objective criteria have been proposed by the M. D. Anderson Cancer Center Pancreas Cancer Group in an attempt to better define the term “borderline resectable” and to guide treatment decisions regarding the use of neoadjuvant therapy and the high likelihood of vein resection and reconstruction as a means to improve the rate of a complete and margin-negative resection.23 Radiographic findings of tumor abutment on the portal vein or SMV with or without venous deformity, and limited encasement of the mesenteric vein and portal vein (i.e., short segment occlusion with suitable vessel for anastomosis above and below) represent the extent of venous involvement that would categorize a tumor as borderline resectable. Radiographic findings suggesting borderline arterial involvement as defined by M. D. Anderson Cancer Center include encasement of a short segment of the hepatic artery, without evidence of tumor extension to the celiac axis and/or tumor abutment of the SMA involving < 180° of the artery circumference. In patients without clinically important major comorbidities, and in the absence of radiographic findings to suggest metastatic disease or locally advanced unresectable disease as outlined above, surgical resection should be considered feasible and likely to be achievable. Whether these resections would result in a higher-than-expected rate of margin-positive resections, and whether such resections would affect survival would best be determined by careful examination of outcomes relative to extent of vascular involvement using objective criteria to determine categorization of extent of disease. Consensus Statement 1. Tumors considered localized and resectable should demonstrate the following: a. No distant metastases. b. No radiographic evidence of SMV and portal vein abutment, distortion, tumor thrombus, or venous encasement. c. Clear fat planes around the celiac axis, hepatic artery, and SMA. 2. Tumors considered borderline resectable include the following: a. No distant metastases. b. Venous involvement of the SMV/portal vein demonstrating tumor abutment with or without impingement and narrowing of the lumen, encasement of the SMV/portal vein but without encasement of the nearby arteries, or short segment venous occlusion resulting from either tumor thrombus or encasement but with suitable vessel proximal and distal to the area of vessel involvement, allowing for safe resection and reconstruction. c. Gastroduodenal artery encasement up to the hepatic artery with either short segment encasement or direct abutment of the hepatic artery, without extension to the celiac axis. d. Tumor abutment of the SMA not to exceed >180° of the circumference of the vessel wall.

Mitotic clonal expansion: A synchronous process required for adipogenesis

Abstract: When induced to differentiate, growth-arrested 3T3-L1 preadipocytes synchronously reenter the cell cycle and undergo mitotic clonal expansion (MCE) followed by expression of genes that produce the adipocyte phenotype. The preadipocytes traverse the G1/S checkpoint synchronously as evidenced by the expression/activation of cdk2-cyclin-E/A, turnover of p27/kip1, hyperphosphorylation of Rb, translocation of cyclin D1 from nuclei to cytoplasm and GSK-3β from cytoplasm to nuclei, and incorporation of [3H]thymidine into DNA. As the cells cross the G1/S checkpoint, C/EBPβ acquires DNA-binding activity, initiating a cascade of transcriptional activation that culminates in the expression of adipocyte proteins. The mitogen-activated protein kinase/extracellular signal-regulated kinase kinase (MEK) inhibitor PD98059 delays, but does not block, MCE and differentiation, the extent of the delay causing a comparable delay in the expression of cell-cycle markers, MCE, and adipogenesis. The more potent and specific MEK inhibitor UO126 and the cyclin-dependent kinase inhibitor roscovitine, which inhibit the cell cycle at different points, block MCE, expression of cell cycle and adipocyte markers, as well as adipogenesis. These results show that MCE is a prerequisite for differentiation of 3T3-L1 preadipocytes into adipocytes.

Neonatal Abstinence Syndrome after Methadone or Buprenorphine Exposure

Abstract: Background Methadone, a full mu-opioid agonist, is the recommended treatment for opioid dependence during pregnancy. However, prenatal exposure to methadone is associated with a neonatal abstinence syndrome (NAS) characterized by central nervous system hyperirritability and autonomic nervous system dysfunction, which often requires medication and extended hospitalization. Buprenorphine, a partial mu-opioid agonist, is an alternative treatment for opioid dependence but has not been extensively studied in pregnancy. Methods We conducted a double-blind, double-dummy, flexible-dosing, randomized, controlled study in which buprenorphine and methadone were compared for use in the comprehensive care of 175 pregnant women with opioid dependency at eight international sites. Primary outcomes were the number of neonates requiring treatment for NAS, the peak NAS score, the total amount of morphine needed to treat NAS, the length of the hospital stay for neonates, and neonatal head circumference. Results Treatment wa...

Epigenetic Determinants of Cancer

Abstract: SUMMARYEpigenetic changes are present in all human cancers and are now known to cooperate with genetic alterations to drive the cancer phenotype. These changes involve DNA methylation, histone modifiers and readers, chromatin remodelers, microRNAs, and other components of chromatin. Cancer genetics and epigenetics are inextricably linked in generating the malignant phenotype; epigenetic changes can cause mutations in genes, and, conversely, mutations are frequently observed in genes that modify the epigenome. Epigenetic therapies, in which the goal is to reverse these changes, are now one standard of care for a preleukemic disorder and form of lymphoma. The application of epigenetic therapies in the treatment of solid tumors is also emerging as a viable therapeutic route.

Regional Distribution of Opiate Receptor Binding in Monkey and Human Brain

Abstract: The frequency of opiate receptors varies dramatically throughout the human and monkey brain. The authors describe a relationship between the distribution of opiate receptors and of neurotransmitters.