Advances and new perspectives in the treatment of metastatic colon cancer

During the last decade we have witnessed an unprecedented outburst of new treatment approaches for the management of metastatic colon cancer. Anti-angiogenic drugs, epidermal growth factor receptor blockers and multi-kinase inhibitors have all resulted in small but consistent improvement in clinical outcomes. However, this progress has paradoxically leaded us into new challenges. In many cases the clinical development was done in parallel and the lack of head-to-head comparison evolved into circumstances where several valid new “standards of care” are available. Even though desirable in essence, the availability of many options as well as different possible combinations frequently leaves the busy clinician in the difficult situation of having to choose between one or the other, sometimes without solid evidence to support each decision. In addition, progress never stops and new agents are continuously tested. For these reason this review will try to summarize all the clinical trials that constitute the theoretical framework that support our daily practice but will also procure the reader with rational answers to common clinical dilemmas by critically appraising the current literature. Lastly, we will provide with a compilation of promising new agents that may soon become our next line of defense against this deadly disease.     

A small fraction of dermatan sulfate with significantly increased anticoagulant activity was selected by interaction with the first complement protein

Dermatan sulfate (DS) is a member of the family of structurally complex, sulfated, linear heteropolysaccharides called glycosaminoglycans (GAGs). It has a similar structure to heparin and heparan sulfate (HS), but with acetylgalactosamine replacing glucosamine, and the uronic acid moiety, mainly iduronic, joined 1-->3 to the hexosamine. We are studying the relationships between structure and activities of dermatan sulfate, in particular those associated with the thrombin inhibition mediated by heparin cofactor II (HCII). As we have demonstrated with heparin, a small fraction of dermatan sulfate was isolated by precipitation with the first component of the complement system, under very specific conditions of low ionic strength, and the presence of calcium ions. The sulfate content and the anticoagulant activity of the dermatan sulfate fraction isolated in the precipitate were three and four times greater respectively than the starting material. Our in vivo studies showed that this fraction has threefold higher thrombolytic activity than the DS. All these results suggest that this fraction could be used as a therapeutic agent for thrombi dissolution.     

X-ray computed tomography of lumbosacral roots and primary hypertrophic neuritis (Dejerine-Sottas disease)

CT without contrast of lumbosacral nerve roots was performed in 13 patients with peroneal atrophy and 28 control subjects. Two series of 5 mm serial sections parallel to the plane of the disk were examined at the L4-L5 and L5-S1 levels, and the transverse diameter of the S1 nerve roots measured at the lower part of the lateral recess. Results showed frank bilateral, grossly symmetrical hypertrophy of lumbosacral roots in 8 of the 13 patients. This hypertrophy involved all roots examined (L4, L5, S1), except in one case where only S1 roots were involved. Hypertrophy was often more marked on the distal part of the roots and on spinal nerves, contrasting with the sometimes normal or only slightly altered appearance of the nerve roots emerging from the dural sac. In these 8 cases, the diameter of the S1 nerve roots was 8 to 18 mm, in contrast to a mean of 3.5 +/- 1 mm in the 28 controls. CT scan images were normal in the remaining 5 patients. The presence of a CT image of nerve hypertrophy was in all cases associated with a marked fall in nerve conduction rate (median nerve motor conduction rate less than 25 msec-1), and a decrease in number of myelinated fibers with numerous onion bulbs. In contrast, the absence of CT nerve hypertrophy could not predict the results of electrophysiological and histological examinations.     

Menzel's hereditary ataxia with slow eye movements and myoclonus: A clinico-pathological study

The patient we describe had cerebellar ataxia, slow eye movements, myoclonus, facial dystonia and signs of spinal cord and peripheral nerve involvement. The patient's mother, brother and sister died from the same disease. Neuropathological examination revealed lesions of olivo-ponto-cerebellar atrophy (OPCA) associated with spinal cord degenerative changes characteristic of Menzel's hereditary ataxia.Although myoclonus was similar to Hunt's dyssynergia cerebellaris myonica, pathological findings did not show significant involvement of the dentate nucleus or superior cerebellar peduncle and physiopathological hypotheses for myoclonus are discussed.Slow eye movement is emphasized in the propositus and we suggest that it could be specific of one type of OPCA. Its pathological significance is discussed, but a primitive and unique involvement of the paramedian pontine reticular formation is unlikely.