Clinicopathological features of extramedullary recurrence/relapse of multiple myeloma

Extramedullary relapses of multiple myeloma (MM) during the course of disease are rare. We report a series of six patients with primary intramedullary MM that were treated with immunomodulatory therapy and/or stem cell transplant, and that later developed extramedullary relapses at various body sites. These six cases represent 3.9% of the 156 patients treated for MM at our institution over a 9-yr period (1999-2007). Five (83.3%) of the six cases showed immature/high-grade histology in the extramedullary relapses as compared with their antecedent MM. The neural cell adhesion molecule, CD56, was immunohistochemically demonstrable in 75% (three of four) of the original myelomas tested, but was absent in 83.3% (five of six) of their extramedullary relapses. The disease typically behaved aggressively and was rapidly fatal in all six patients even when therapy was administered. The median time of progression to extramedullary relapse was 29 months (range 9-64 months), and the median survival after diagnosis of the relapses was only 38 d (range 1-106 d). Our case series shows that extramedullary relapse of MM is characterized by high-grade histology, loss of CD56 expression, frequent resistance to current therapeutic regimens, aggressive biological behavior, and very short survival.     

Neuropharmacology of alcohol addiction

Despite the generally held view that alcohol is an unspecific pharmacological agent, recent molecular pharmacology studies demonstrated that alcohol has only a few known primary targets. These are the NMDA, GABA(A), glycine, 5-hydroxytryptamine 3 (serotonin) and nicotinic ACh receptors as well as L-type Ca(2+) channels and G-protein-activated inwardly rectifying K(+) channels. Following this first hit of alcohol on specific targets in the brain, a second wave of indirect effects on a variety of neurotransmitter/neuropeptide systems is initiated that leads subsequently to the typical acute behavioural effects of alcohol, ranging from disinhibition to sedation and even hypnosis, with increasing concentrations of alcohol. Besides these acute pharmacodynamic aspects of alcohol, we discuss the neurochemical substrates that are involved in the initiation and maintenance phase of an alcohol drinking behaviour. Finally, addictive behaviour towards alcohol as measured by alcohol-seeking and relapse behaviour is reviewed in the context of specific neurotransmitter/neuropeptide systems and their signalling pathways. The activity of the mesolimbic dopaminergic system plays a crucial role during the initiation phase of alcohol consumption. Following long-term, chronic alcohol consumption virtually all brain neurotransmission seems to be affected, making it difficult to define which of the systems contributes the most to the transition from controlled to compulsive alcohol use. However, compulsive alcohol drinking is characterized by a decrease in the function of the reward neurocircuitry and a recruitment of antireward/stress mechanisms comes into place, with a hypertrophic corticotropin-releasing factor system and a hyperfunctional glutamatergic system being the most important ones.     

Neuroplasticity in the mesolimbic dopamine system and cocaine addiction

The main characteristics of cocaine addiction are compulsive drug use despite adverse consequences and high rates of relapse during periods of abstinence. A current popular hypothesis is that compulsive cocaine use and cocaine relapse is due to drug-induced neuroadaptations in reward-related learning and memory processes, which cause hypersensitivity to cocaine-associated cues, impulsive decision making and abnormal habit-like learned behaviours that are insensitive to adverse consequences. Here, we review results from studies on the effect of cocaine exposure on selected signalling cascades, growth factors and physiological processes previously implicated in neuroplasticity underlying normal learning and memory. These include the extracellular signal-regulated kinase (ERK) signalling pathway, brain-derived neurotrophic factor (BDNF), glutamate transmission, and synaptic plasticity (primarily in the form of long-term potentiation and depression, LTP and LTD). We also discuss the degree to which these cocaine-induced neuroplasticity changes in the mesolimbic dopamine system mediate cocaine psychomotor sensitization and cocaine-seeking behaviours, as assessed in animal models of drug addiction. Finally, we speculate on how these factors may interact to initiate and sustain cocaine psychomotor sensitization and cocaine seeking.     

Cohort Study on the Effect of a Combined Treatment of Traditional Chinese Medicine and Western Medicine on the Relapse and Metastasis of 222 Patients with Stage Ⅱ and Ⅲ Colorectal Cancer after Radical Operation

Objective： To evaluate the effectiveness of a comprehensive therapy of traditional Chinese medicine （TCM） in reducing the relapse and metastasis of stage Ⅱ and Ⅲ colorectal cancer based on conventional Western medicine （WM） therapy. Methods： Two hundred and twenty-two patients in total, diagnosed as stage Ⅱ and Ⅲ colorectal cancer from February 2000 to March 2006, were recruited from Xiyuan Hospital, China Academy of Chinese Medical Sciences and the General Hospital of Beijing Military Area. They were followed-up once every 3-6 months. Twenty cases dropped out from the cohort. The remaining 202 patients were all treated with routine WM treatment [including R0 radical operation, or chemotherapy or/and radiotherapy according to national comprehensive cancer network （NCCN） clinical guidelines]. These patients were assigned to two groups based on whether or not they were additionally treated with TCM comprehensive therapy （orally administered with a decoction according to syndrome differentiation, combined with a traditional patent drug over one year）. Ninety-eight patients from Xiyuan Hospital were treated with WM and TCM （combined group）, and 104 patients from the General Hospital of Beijing Military Area were treated with WM alone （WM group）. The demographic data at baseline were comparable, including the operation times, age, sex, TNM staging, and pathological types. The patients were followed-up for one to five years. Up to now, there are 98, 98, 77, 64, and 47 patients with 1, 2, 3, 4, and 5 years of follow-up in the combined group, respectively; and 104, 104, 97, 81, and 55 patients in the WM group, respectively. The results of the 5-year follow-up of all the patients will be available in 2011. Results： The relapse/metastasis rate of 1-, 2-, 3-, 4-, and 5-year were 0 （0/98）, 2.04% （2/98）, 11.69% （9/77）, 14.06% （9/64）, and 21.28% （10/47） in the combined group, and were 4.80%（5/104）, 16.35% （17/104）, 21.65% （21/97）, 25.93% （21/81）, and 38.     

Anger Expression Style Predicts the Domain of the First Smoking Relapse After a Quit Attempt

Background: Risk for smoking relapse may be associated with context-dependent social and behavioral cues. However, lack of research examining the role of trait negative mood such as anger in this relationship and assessment of objective indices related to smoking status (e.g., biochemical measures) may limit existing findings. We examined the roles of trait anger, habitual anger expression behavior, and the situation in which the first incident of smoking lapse following a quit attempt occurs. Methods: One-hundred and five smokers interested in cessation (mean age, SD: 34.7 ± 11.8) set a quit day and attended multiple post-quit assessments where they were asked to provide biochemical measures including exhaled carbon monoxide (CO) and self-report measurements, including smoking status. Results: Eighty-eight participants (40 women) returned to smoking over the 12-month study period. Self-reported smoking status was verified by exhaled CO measurements. Thirty-one percent of participants who relapsed reported the first lapse occurring at home, 15% at work, 14% at a restaurant or a bar, and 8% in a car. Multinomial logistic regression models found that high levels of anger-out were associated with smoking relapse in situations other than work or home (p <.05). Conclusions: These results expand prior work suggesting habitual anger expression style may moderate associations between situational factors and risk for smoking relapse, highlighting the need to incorporate findings in treatment methods. Absence of gender differences suggests the situational factors explored here affect relapse independent of gender.     

Stopping the “revolving door”: “Zeida Laderech,” a unique rehabilitation house for young adults with severe and enduring eating disorders

A failure to maintain improvement achieved during acute treatment, followed by a “revolving door syndrome,” is a common phenomenon in eating disorders (EDs). As a result, many patients develop a chronic course that is difficult to treat. To target these difficulties, we established a novel rehabilitation treatment model in Israel for patients with severe and enduring EDs, based on the “recovery theory” in mental health treatment. This paper describes the process of conceiving this model and specifies the components of this rehabilitation house, “Zeida Laderech” (Provisions for the Journey), that aims to provide a home-like environment, while assisting in developing a healthy and balanced lifestyle. Finally, the model is discussed in light of other residential programs established in the world. With the hope to improve the overall prognosis of individuals with EDs, it is suggested that the similar programs and ongoing innovation will continue to emerge internationally.     

Analysis by array CGH of genomic changes associated with the progression or relapse of Wilms' tumour

Despite aggressive salvage regimens, approximately half of all children who suffer a Wilms' tumour recurrence will die of their disease. Although there are increasing data on molecular genetic prognostic factors present in the tumour at diagnosis, there is little information regarding the molecular events that occur with Wilms' tumour progression and relapse. In the present study, microarray-based comparative genomic hybridization (aCGH) analysis has been carried out on 58 Wilms' tumour samples, which included 38 untreated primary and 20 recurrent tumours. A higher degree of copy number changes was observed in the recurrent tumours (33.0% genomic clones) than in the primary tumour (21.2%). Paired analysis highlighted the acquisition of 15q gain with high levels of IGF1R expression in the tumour recurrence in two cases. The most statistically significant abnormality acquired between diagnosis and relapse was loss of 17p. One case that experienced 17p loss was classified as favourable histology at diagnosis, but exhibited diffuse anaplasia at recurrence and had a homozygous TP53 deletion. Another instructive case with a constitutional 11p13 deletion presented with bilateral tumours and suffered two subsequent recurrences in the left kidney. A somatic WT1 mutation was found only in the right kidney tumour, while the constitutional 11p13 deletion was the only abnormality detected in the initial left kidney tumour by aCGH. The two subsequent relapses in the left kidney contained an accumulation of additional genetic alterations, including an independent WT1 mutation.     

The role of different subregions of the basolateral amygdala in cue-induced reinstatement and extinction of food-seeking behavior

Reinstatement of previously extinguished instrumental responding for drug-related cues has been used as an animal model for relapse of drug abuse, and is disrupted by inactivation of the basolateral amygdala (BLA). However, the role that the BLA plays in reinstatement induced by cues associated with natural rewards is unclear. The present study assessed the effects of inactivation of different regions of the BLA in cue-induced reinstatement of food-seeking behavior and in the extinction of instrumental responding for food. In experiment 1, rats acquired a lever pressing response for food reward paired with a light/tone conditioned stimulus (CS). They were then subjected to extinction training, where both food and the CS were withheld. Reinstatement of extinguished responding was measured during response-contingent presentations of the CS alone. Following saline infusions into the caudal or rostral BLA, rats displayed a significant increase in lever pressing during reinstatement sessions. Inactivation of these subregions with bupivacaine did not attenuate responding for the CS in the absence of food delivery. In fact, inactivation of the caudal BLA potentiated responding relative to vehicle treatments. Analysis of within-session responding revealed that caudal BLA inactivation retarded extinction of lever pressing in response to the CS. In experiment 2, inactivation of the caudal BLA on the first or second day of extinction training significantly retarded the acquisition of extinction learning on the following day. These data indicate that that the caudal BLA may play a specific role in the extinction of appetitive conditioned responses, by monitoring changes in the reinforcing value of pavlovian conditioned stimuli linked to action-outcome associations once these associations have been formed. Moreover, these findings support a growing body of evidence indicating that separate neural circuits incorporating the BLA may play different roles in mediating reinstatement of reward-seeking behaviors induced by either drug or food related stimuli.     

Radiothérapie de rattrapage après prostatectomie radicale : que faire en cas de concentration de PSA postopératoire élevée persistante ou de récidive locale macroscopique ?

The management of the postoperative biological relapse of prostate cancer is most often based on salvage radiotherapy (RT) and a variable duration of hormone therapy (HT) in addition. The indications for RT ± HT become more consensual for the adjuvant postoperative situation or in the event of a rising PSA level after a period where an undetectable PSA level was achieved. On the other hand, in the event of detectable PSA immediately postoperatively or in the event of a biological recurrence with macroscopic relapse in the prostate bed seen on conventional imaging assessment, the treatment options are still being evaluated. This article will describe these 2 situations and their current management but also will come through assessments with the contribution of modern imaging and new treatment options in terms of RT dose and RT ± HT combination.