Benign and malignant tumors of the rectum and perirectal region

Although most rectal masses are histologically characterized as adenocarcinomas, the rectum and perirectal region can be affected by a wide variety of tumors and tumor-like conditions that can mimic the symptoms caused by rectal adenocarcinoma, including mucosal or submucosal rectal tumors such as lymphoma, gastrointestinal stromal tumor, leiomyosarcoma, neuroendocrine tumor, hemangioma, and melanoma, as well as tumors of the perirectal region such as developmental cyst, neurogenic tumor, osseous tumor, and other miscellaneous conditions. As a group, tumors of the rectum are considerably different from the group of tumors that arise in the perirectal region: they are most often neoplastic, symptomatic, and malignant, whereas tumors arising in the perirectal region are most commonly congenital, asymptomatic, and benign. Proctoscopy with biopsy is the most important method for the diagnosis of rectal tumors, but this procedure cannot determine the precise intramural extension of a rectal tumor and cannot accurately distinguish submucosal and intramural tumors from extramural tumors. Cross-sectional imaging, especially transrectal ultrasound and magnetic resonance imaging, allows evaluation of the entire bowel wall thickness and the perirectal tissues, helping further characterize these tumors. Recognition of the existence of these masses and their key clinical and imaging features is crucial for clinicians to accurately diagnose and appropriately manage these conditions.     

Steroid-Mediated Decrease in Blood Mesenchymal Stem Cells in Liver Transplant could Impact Long-Term Recovery

Orthotopic liver transplant (OLT) remains the standard of care for end stage liver disease. To circumvent allo-rejection, OLT subjects receive gluococorticoids (GC). We investigated the effects of GC on endogenous mesenchymal stem (stromal) cells (MSCs) in OLT. This question is relevant because MSCs have regenerative potential and immune suppressor function. Phenotypic analyses of blood samples from 12 OLT recipients, at pre-anhepatic, anhepatic and post-transplant (2 h, Days 1 and 5) indicated a significant decrease in MSCs after GC injection. The MSCs showed better recovery in the blood from subjects who started with relatively low MSCs as compared to those with high levels at the prehepatic phase. This drop in MSCs appeared to be linked to GC since similar change was not observed in liver resection subjects. In order to understand the effects of GC on decrease MSC migration, in vitro studies were performed in transwell cultures. Untreated MSCs could not migrate towards the GC-exposed liver tissue, despite CXCR4 expression and the production of inflammatory cytokines from the liver cells. GC-treated MSCs were inefficient with respect to migration towards CXCL12, and this correlated with retracted cytoskeleton and motility. These dysfunctions were partly explained by decreases in the CXCL12/receptor axis. GC-associated decrease in MSCs in OLT recipients recovered post-transplant, despite poor migratory ability towards GC-exposed liver. In total, the study indicated that GC usage in transplant needs to be examined to determine if this could be reduced or avoided with adjuvant cell therapy.     

Regeneration of skeletal and cardiac muscle in mammals: do nonprimate models resemble human pathology?

Most of the available information regarding the regenerative potential and compensatory remodeling of mammalian tissues has been obtained from nonprimate animals, mainly rodent experimental models. The increasing use of transgenic mice for studies of the mechanisms controlling organogenesis and regeneration also requires a clear understanding of their applicability as experimental models for studies of similar processes in humans and other mammals. Application of modern cell biology methods to studies of regenerative processes has provided new insights into similarity and differences in cellular responses to injury in the tissues of different mammalian species. During more than 200-million years of progressive divergent evolution of mammals, cellular mechanisms of tissue regeneration and compensatory remodeling evolved together with increasingly adaptive functional specialization and structural complexity of mammalian tissues and organs. Rodents represent a phylogenetically ancient order of mammals that has conservatively retained a number of morphofunctional characteristics of early representatives of this class, which include enhanced regenerative capacity of tissues. A comparative analysis of regenerative processes in skeletal and cardiac muscle, as well as in several other mammalian tissues, shows that time courses and intensities of regeneration in response to the same type of injury vary even within taxonomically related species (e.g., rat, mouse, and hamster). The warm bloodedness of mammals facilitated the development of more complex mechanisms of metabolic, immune, and neurohumoral regulation, which resulted in a stronger dependence of regenerative processes on vascularization and innervation. For this reason, interspecies modifications of regenerative responses are limited by the capacity of the animal to resorb rapidly the foci of necrosis and to revascularize and reinnervate the volume of the regenerating tissue. These differences, among other factors, result in significantly lower rates of reparative regeneration in mammals possessing larger body sizes than rodents. A review of these data strongly indicates that the phylogenetic age and biological differences between different species should be taken into account before extrapolation of regenerative properties of nonprimate tissues on the regenerative responses in the primates.     

Pregnancy during TNFα antagonist therapy: Beware the rifampin-oral contraceptive interaction. Report of two cases

We report two cases of pregnancy in patients taking TNFα antagonists for chronic inflammatory joint disease. A factor in both pregnancies was the use of rifampin concomitantly with a combined oral contraceptive. Both patients were taking rifampin and isoniazid for tuberculosis prophylaxis in compliance with French recommendations for patients with positive intradermal tuberculin tests who are scheduled to receive biotherapeutic agents.